Abbreviated Solutions to Problems

Fuller solutions to all chapter problems are published in the Absolute molecules also differ in size and shape—either of these property Ultimate Study Guide to Accompany Principles of Biochemistry. differences could be the basis for separation. (b) Glucose is a For all numerical problems, answers are expressed with the correct smaller molecule than a nucleotide; separation could be based on number of signifi cant fi gures. size. The nitrogenous base and/or the phosphate group also endows nucleotides with characteristics (solubility, charge) that Chapter 1 could be used for separation from glucose. 1. (a) Diameter of magnified cell 5 500 mm (b) 2.7 3 1012 actin 10. It is improbable that silicon could serve as the central organizing 10 molecules (c) 36,000 mitochondria (d) 3.9 3 10 glucose element for life, especially in an O2-containing atmosphere such molecules (e) 50 glucose molecules per hexokinase molecule as that of Earth. Long chains of silicon atoms are not readily 2. (a) 1 3 10212 g 5 1 pg (b) 10% (c) 5% synthesized; the polymeric macromolecules necessary for more 3. (a) 1.6 mm; 800 times longer than the cell; DNA must be tightly complex functions would not readily form. Oxygen disrupts coiled. (b) 4,000 proteins bonds between silicon atoms, and silicon–oxygen bonds are extremely stable and difficult to break, preventing the breaking 4. (a) Metabolic rate is limited by diffusion, which is limited by and making of bonds that is essential to life processes. surface area. (b) 12 mϪ1 for the bacterium; 0.04 mϪ1 for the amoeba; surface-to-volume ratio 300 times higher in the 11. Only one enantiomer of the drug was physiologically active. bacterium. Dexedrine consisted of the single enantiomer; Benzedrine consisted of a racemic mixture. 5. 2 3 106 s (about 23 days) 12. (a) 3 Phosphoric acid groups; -D-ribose; guanine (b) Choline; 6. The vitamin molecules from the two sources are identical; the phosphoric acid; glycerol; oleic acid; palmitic acid (c) Tyrosine; body cannot distinguish the source; only associated impurities 2 glycines; phenylalanine; methionine might vary with the source. 13. (a) CH O; C H O 7. 2 3 6 3 (b) (a) H HH(b) OH H OH ϩ H OH OH H N C C OH HCOH 3 H C C H C C H C C H H HCOHHydroxyls H C OH H C OH H C OH Amino Hydroxyl H C OH HO HO H H 123

OH OH H OH (c) O (d) COOϪ Carboxyl OH H O ϩ HO C C HO C C HCCC HO P OϪ Phosphoryl Amino HC H3N H C H H C OH H H OH O HCOH Hydroxyl H H H C C COOϪ CH 3 456 H Carboxyl Methyl

HO H O HO OH O H OH O (e) ϪO O (f) H O HCCC HCCC HCCC Carboxyl Aldehyde C C H H OH H H H H OH H ϩ CH CH NH Amino 2 3 789

CH2 Hydroxyl HO C H NH H C OH HO H HO O OH H O OH Amido O C O H C OH Hydroxyls HCC C H C C HC H C C C H HO H H H H H OH H C OH Hydroxyl CH2OH

Methyl H3C C CH3 Methyl 10 11 12

CH2OH Hydroxyl (c) X contains a chiral center; eliminates all but 6 and 8. (d) X contains an acidic functional group; eliminates 8; structure 6 is 8. OH H H consistent with all data. (e) Structure 6; we cannot distinguish between the two possible enantiomers. HO C* CH N C CH 2 3 14. The compound shown is (R)-propranolol; the carbon bearing the H CH HO 3 hydroxyl group is the chiral carbon. (S)-Propranolol has the structure: The two enantiomers have different interactions with a chiral biological “receptor” (a protein). 9. (a) Only the amino acids have amino groups; separation could be ON* based on the charge or binding affinity of these groups. Fatty acids H OH are less soluble in water than amino acids, and the two types of AS-1 AS-2 Abbreviated Solutions to Problems

15. The compound shown is (S,S)-methylphenidate. (R,R)- H Br OH N C H methylphenidate has the structure: H + 9 17 H N O Br H HO O Br HN H O HO H H O N O OH O Br 2 * NH H OH HO O * H H Tetrabromosucrose Sucronic acid

(d) First, each molecule has multiple AH-B groups, so it is difficult to know which is the important one. Second, because The chiral carbons are indicated with asterisks. the AH-B motif is very simple, many nonsweet molecules will have this group. (e) Sucrose and deoxysucrose. Deoxysucrose 16. (a) A more negative DG8 corresponds to a larger K for the eq lacks one of the AH-B groups present in sucrose and has a binding reaction, so the equilibrium is shifted more toward slightly lower MRS than sucrose—as is expected if the AH-B products and tighter binding—and thus greater sweetness and groups are important for sweetness. (f) There are many such higher MRS. (b) Animal-based sweetness assays are time- examples; here are a few: (1) D-Tryptophan and 6-chloro-D- consuming. A computer program to predict sweetness, even if tryptophan have the same AH-B group but very different MRS not always completely accurate, would allow chemists to design values. (2) Aspartame and neotame have the same AH-B groups effective sweeteners much faster. Candidate molecules could but very different MRS values. (3) Neotame has two AH-B then be tested in the conventional assay. (c) The range 0.25 to groups and alitame has three, yet neotame is more than five 0.4 nm corresponds to about 1.5 to 2.5 single-bond lengths. The times sweeter than alitame. (4) Bromine is less electronegative figure below can be used to construct an approximate ruler; any than oxygen and thus is expected to weaken an AH-B group, yet atoms in the light red rectangle are between 0.25 and 0.4 nm tetrabromosucrose is much sweeter than sucrose. (g) Given from the origin of the ruler. enough “tweaking” of parameters, any model can be made to fit a defined dataset. Because the objective was to create a model to predict DG8 for molecules not tested in vivo, the researchers There are many possible AH-B groups in the molecules; a few needed to show that the model worked well for molecules it had are shown here. not been trained on. The degree of inaccuracy with the test set could give researchers an idea of how the model would behave H OH for novel molecules. (h) MRS is related to Keq, which is related H exponentially to DG8, so adding a constant amount to DG8 O HO H H O OH multiplies the MRS by a constant amount. Based on the values H H given with the structures, a change in DG8 of 1.3 kcal/mol HO H OH OH O corresponds to a 10-fold change in MRS. H OH H Deoxysucrose Chapter 2 1. Ethanol is polar; ethane is not. The ethanol OOH group can H OH hydrogen-bond with water. H O HO H HO O OH 2. (a) 4.76 (b) 9.19 (c) 4.0 (d) 4.82 H Ϫ4 Ϫ7 Ϫ12 HO H H 3. (a) 1.51 3 10 M (b) 3.02 3 10 M (c) 7.76 3 10 M OH O OH H OH 4. 1.1 H 5. (a) HCl Δ H1 1 Cl2 (b) 3.3 (c) NaOH Δ Na1 1 OH2 Sucrose (d) 9.8

NH2 O 6. 1.1 O H O N 7. 1.7 3 10Ϫ9 mol of acetylcholine O OH OH S 8. 0.1 M HCl NH O O O NH2 9. (a) greater (b) higher (c) lower N 10. 3.3 mL H O CH3 11. (a) RCOOϪ (b) RNH (c) H POϪ (d) HCOϪ D-Tryptophan Saccharin Aspartame 2 2 4 3 12. (a) 5.06 (b) 4.28 (c) 5.46 (d) 4.76 (e) 3.76 O 13. (a) 0.1 M HCl (b) 0.1 M NaOH (c) 0.1 M NaOH NH2 O Ϫ OH H H 14. (d) Bicarbonate, a weak base, titrates OOH to OO , making N N S OH the compound more polar and more water-soluble. NH2 15. Stomach; the neutral form of aspirin present at the lower pH is Cl N O O H less polar and passes through the membrane more easily. 6-Chloro-D-tryptophan Alitame 16. 9 17. 7.4

18. (a) pH 8.6 to 10.6 (b) 4/5 (c) 10 mL (d) pH 5 pKa 2 2 NH O H 19. 8.9 N OH 20. 2.4 O 21. 6.9 O O 22. 1.4

CH3 23. NaH2PO4 ? H2O, 5.8 g/L; Na2HPO4, 8.2 g/L Ϫ Neotame 24. [A ]/[HA] 5 0.10 AbbreviatedSolutionsToProblems.indd Page AS-3 05/10/12 10:59 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-3

25. Mix 150 mL of 0.10 M sodium acetate and 850 mL of 0.10 M 4. (a)–(c) acetic acid. COOH 26. Acetic acid; its pK is closest to the desired pH. HN ϩ pK ϭ 1.82 a CH CH NH 1 27. (a) 4.6 (b) 0.1 pH unit (c) 4 pH units ϩ 2 3 N Hϩ 28. 4.3 H 29. 0.13 M acetate and 0.07 M acetic acid 1 30. 1.7 31. 7 COOϪ ϩ 32. (a) HN pKR ϭ 6.0 CH CH NH ϩ 2 3 COOH COO N Hϩ H H3N C H H2N C H 2

CH3 CH3 Ϫ Fully protonated Fully deprotonated COO

HN ϩ pK2 ϭ 9.17 (b) fully protonated (c) zwitterion (d) zwitterion (e) fully CH2 CH NH3 deprotonated N Hϩ 33. (a) Blood pH is controlled by the carbon dioxide–bicarbonate 3 1 2 buffer system, CO2 1 H2O Δ H 1 HCO3 . During Ϫ hypoventilation, [CO2] increases in the lungs and arterial blood, COO ϩ driving the equilibrium to the right, raising [H ] and lowering HN CH CH NH pH. (b) During hyperventilation, [CO2] decreases in the lungs 2 2 and arterial blood, reducing [Hϩ] and increasing pH above the N normal 7.4 value. (c) Lactate is a moderately strong acid, 4 completely dissociating under physiological conditions and thus lowering the pH of blood and muscle tissue. Hyperventilation pH Structure Net charge Migrates toward removes Hϩ, raising the pH of blood and tissues in anticipation of the acid buildup. 1 1 12 Cathode 34. 7.4 4 2 11 Cathode 8 3 0 Does not migrate 35. Dissolving more CO in the blood increases [Hϩ] in blood and 2 12 4 21 Anode extracellular fluids, lowering pH: CO2(d) 1 H2O Δ 1 2 H2CO3 Δ H 1 HCO3 36. (a) Use the substance in its surfactant form to emulsify the 5. (a) Asp (b) Met (c) Glu (d) Gly (e) Ser spilled oil, collect the emulsified oil, then switch to the 6. (a) 2 (b) 4 (c) nonsurfactant form. The oil and water will separate and the oil COOϪ COOϪ COOϪ COOϪ can be collected for further use. (b) The equilibrium lies ϩ ϩ ϩ ϩ strongly to the right. The stronger acid (lower pK ), H CO , a 2 3 H3NHC H3NHC H C NH3 H C NH3 donates a proton to the conjugate base of the weaker acid

(higher pKa), amidine. (c) The strength of a surfactant depends HCHC 3 H3CHC HCHC 3 H3C C H on the hydrophilicity of its head groups: the more hydrophilic, CH CH CH CH the more powerful the surfactant. The amidinium form of s-surf 2 2 2 2 is much more hydrophilic than the amidine form, so it is a more CH3 CH3 CH3 CH3 powerful surfactant. (d) Point A: amidinium; the CO2 has had plenty of time to react with the amidine to produce the 7. (a) Structure at pH 7: amidinium form. Point B: amidine; Ar has removed CO2 from the solution, leaving the amidine form. (e) The conductivity rises as O O O uncharged amidine reacts with CO2 to produce the charged H3N CH C N CH C N CH CO amidinium form. (f) The conductivity falls as Ar removes CO2,

shifting the equilibrium to the uncharged amidine form. CH3 H CH3 H CH3 (g) Treat s-surf with CO2 to produce the surfactant amidinium K K p 2 8.03 p 1 3.39 form and use this to emulsify the spill. Treat the emulsion with Ar to remove the CO2 and produce the nonsurfactant amidine (b) Electrostatic interaction between the carboxylate anion and form. The oil will separate from the water and can be recovered. the protonated amino group of the alanine zwitterion favorably affects the ionization of the carboxyl group. This favorable Chapter 3 electrostatic interaction decreases as the length of the poly(Ala) 1. L; determine the absolute configuration at the carbon and increases, resulting in an increase in pK1. (c) Ionization of the compare it with D- and L-glyceraldehyde. protonated amino group destroys the favorable electrostatic 2. (a) I (b) II (c) IV (d) II (e) IV (f) II and IV (g) III (h) III interaction noted in (b). With increasing distance between the (i) V (j) III (k) V (l) II (m) III (n) V (o) I, III, and V charged groups, removal of the proton from the amino group in poly(Ala) becomes easier and thus pK2 is lower. The 3. (a) pI . pKa of the -carboxyl group and pI , pKa of the -amino group, so both groups are charged (ionized). (b) 1 in intramolecular effects of the amide (peptide bond) linkages keep 2.19 3 107. The pI of alanine is 6.01. From Table 3–1 and the pKa values lower than they would be for an alkyl-substituted amine. Henderson-Hasselbalch equation, 1/4,680 carboxyl groups and 8. 75,000 1/4,680 amino groups are uncharged. The fraction of alanine 9. (a) 32,000. The elements of water are lost when a peptide bond molecules with both groups uncharged is the product of these forms, so the molecular weight of a Trp residue is not the same fractions. as the molecular weight of free tryptophan. (b) 2 AbbreviatedSolutionsToProblems.indd Page AS-4 05/10/12 10:59 AM user-F408 /Users/user-F408/Desktop

AS-4 Abbreviated Solutions to Problems

10. The protein has four subunits, with molecular masses of 160, 90, Ap15: residues 14–15–16. This is the only Tyr–Glx–Leu in the A 90, and 60 kDa. The two 90 kDa subunits (possibly identical) chain; there is 1 amido group, so the peptide must be Tyr–Gln– are linked by one or more disulfide bonds. Leu: 11. (a) at pH 3, 12; at pH 8, 0; at pH 11, 21 (b) pI 5 7.8 N–Gly–Ile–Val–Glx–Glx–Cys–Cys–Ala–Ser–Val– 12. pI 1; carboxylate groups; Asp and Glu 15 10 13. Lys, His, Arg; negatively charged phosphate groups in DNA Cys–Ser–Leu–Tyr–Gln–Leu–Glx–Asx–Tyr–Cys–Asn–C interact with positively charged side groups in histones. 15 20 14. (a) (Glu) (b) (Lys–Ala) (c) (Asn–Ser–His) 20 3 5 Ap14: residues 14–15–16–17. It has 1 amido group, and we (d) (Asn–Ser–His) 5 already know that residue 15 is Gln, so residue 17 must be Glu: 15. (a) Specific activity after step 1 is 200 units/mg; step 2, 600 N units/mg; step 3, 250 units/mg; step 4, 4,000 units/mg; step 5, –Gly–Ile–Val–Glx–Glx–Cys–Cys–Ala–Ser–Val– 15,000 units/mg; step 6, 15,000 units/mg (b) Step 4 (c) Step 3 15 10 (d) Yes. Specific activity did not increase in step 6; SDS Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asx–Tyr–Cys–Asn–C polyacrylamide gel electrophoresis 15 20 16. (a) [NaCl] 5 0.5 mM (b) [NaCl] 5 0.05 mM. Ap3: residues 18–19–20–21. It has 2 amido groups, and we 17. C elutes first, B second, A last. know that residue 21 is Asn, so residue 18 must be Asn: 18. Tyr–Gly–Gly–Phe–Leu N–Gly–Ile–Val–Glx–Glx–Cys–Cys–Ala–Ser–Val– Leu 19. 15 10 Orn Phe Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn–C Val Pro 15 20 Pro Val Ap1: residues 17–18–19–20–21, which is consistent with residues 18 and 21 being Asn. Phe Orn Leu Ap5pa1: residues 1–2–3–4. It has 0 amido group, so residue 4 must be Glu: The arrows correspond to the orientation of the peptide bonds, N Glu OCO S NHO. –Gly–Ile–Val– –Glx–Cys–Cys–Ala–Ser–Val– 15 10 20. 88%, 97%. The percentage (x) of correct amino acid residues C released in cycle n is xn/x. All residues released in the first cycle Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn– are correct, even though the efficiency of cleavage is not perfect. 15 20 21. (a) Y (1), F (7), and R (9) (b) Positions 4 and 9; K (Lys) is more Ap5: residues 1 through 13. It has 1 amido group, and we know common at 4, R (Arg) is invariant at 9 (c) Positions 5 and 10; E that residue 4 is Glu, so residue 5 must be Gln: (Glu) is more common at both positions (d) Position 2; S (Ser) N–Gly–Ile–Val–Glu–Gln–Cys–Cys–Ala–Ser–Val– 22. (a) peptide 2 (b) peptide 1 (c) peptide 2 (d) peptide 3 15 10 23. (a) Any linear polypeptide chain has only two kinds of free amino Cys–Ser–Leu–Tyr–Gln–Leu–Glu–Asn–Tyr–Cys–Asn–C groups: a single -amino group at the amino terminus, and an -amino group on each Lys residue present. These amino groups 15 20 react with FDNB to form a DNP–amino acid derivative. Insulin gave Chapter 4 two different -amino-DNP derivatives, suggesting that it has two amino termini and thus two polypeptide chains—one with an 1. (a) Shorter bonds have a higher bond order (are multiple rather O amino-terminal Gly and the other with an amino-terminal Phe. than single) and are stronger. The peptide C N bond is Because the DNP-lysine product is -DNP-lysine, the Lys is not at stronger than a single bond and is midway between a single and an amino terminus. (b) Yes. The A chain has amino-terminal Gly; a double bond in character. (b) Rotation about the peptide the B chain has amino-terminal Phe; and (nonterminal) residue 29 bond is difficult at physiological temperatures because of its in the B chain is Lys. (c) Phe–Val–Asp–Glu–. Peptide B1 shows partial double-bond character. that the amino-terminal residue is Phe. Peptide B2 also includes 2. (a) The principal structural units in the wool fiber polypeptide Val, but since no DNP-Val is formed, Val is not at the amino (-keratin) are successive turns of the helix, at 5.4 Å intervals; terminus; it must be on the carboxyl side of Phe. Thus the coiled coils produce the 5.2 Å spacing. Steaming and stretching sequence of B2 is DNP-Phe–Val. Similarly, the sequence of B3 must the fiber yields an extended polypeptide chain with the be DNP-Phe–Val–Asp, and the sequence of the A chain must begin conformation, with a distance between adjacent R groups of Phe–Val–Asp–Glu–. (d) No. The known amino-terminal sequence about 7.0 Å. As the polypeptide reassumes an -helical structure, of the A chain is Phe–Val–Asn–Gln–. The Asn and Gln appear in the fiber shortens. (b) Processed wool shrinks when polypeptide Sanger’s analysis as Asp and Glu because the vigorous hydrolysis in chains are converted from an extended conformation to the step 7 hydrolyzed the amide bonds in Asn and Gln (as well as the native -helical conformation in the presence of moist heat. The peptide bonds), forming Asp and Glu. Sanger et al. could not structure of silkO sheets, with their small, closely packed distinguish Asp from Asn or Glu from Gln at this stage in their amino acid side chains—is more stable than that of wool. analysis. (e) The sequence exactly matches that in Fig. 3–24. Each 3. 42 peptide bonds per second peptide in the table gives specific information about which Asx 4. At pH . 6, the carboxyl groups of poly(Glu) are deprotonated; residues are Asn or Asp and which Glx residues are Glu or Gln. repulsion among negatively charged carboxylate groups leads to Ac1: residues 20–21. This is the only Cys–Asx sequence in the unfolding. Similarly, at pH 7, the amino groups of poly(Lys) are A chain; there is 1 amido group in this peptide, so it must be protonated; repulsion among these positively charged groups Cys–Asn: also leads to unfolding. 5. (a) Disulfide bonds are covalent bonds, which are much stronger N–Gly–Ile–Val–Glx–Glx–Cys–Cys–Ala–Ser–Val– than the noncovalent interactions that stabilize most proteins. 15 10 They cross-link protein chains, increasing their stiffness, Cys–Ser–Leu–Tyr–Glx–Leu–Glx–Asx–Tyr–Cys–Asn–C mechanical strength, and hardness. (b) Cystine residues 15 20 (disulfide bonds) prevent the complete unfolding of the protein. AbbreviatedSolutionsToProblems.indd Page AS-5 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-5

6. 5 (f) and 5 (e). often require chaperones for proper folding; these are not 7. (a) Bends are most likely at residues 7 and 19; Pro residues in present in the study buffer. (7) In cells, HIV protease is the cis configuration accommodate turns well. (b) The Cys synthesized as part of a larger chain that is then proteolytically residues at positions 13 and 24 can form disulfide bonds. processed; the protein in the study was synthesized as a single (c) External surface: polar and charged residues (Asp, Gln, Lys); molecule. (c) Because the enzyme is functional with Aba interior: nonpolar and aliphatic residues (Ala, Ile); Thr, though substituted for Cys, disulfide bonds do not play an important polar, has a hydropathy index near zero and thus can be found role in the structure of HIV protease. (d) Model 1: It would either on the external surface or in the interior of the protein. fold like the L-protease. Argument for: The covalent structure is the same (except for chirality), so it should fold like the 8. 30 amino acid residues; 0.87 L-protease. Argument against: Chirality is not a trivial detail; 9. Myoglobin is all three. The folded structure, the “globin fold,” is three-dimensional shape is a key feature of biological a motif found in all globins. The polypeptide folds into a single molecules. The synthetic enzyme will not fold like the domain, which for this protein represents the entire three- L-protease. Model 2: It would fold to the mirror image of the dimensional structure. L-protease. For: Because the individual components are mirror 10. Protein (a), a barrel, is described by Ramachandran plot (c), images of those in the biological protein, it will fold in the which shows most of the allowable conformations in the upper mirror-image shape. Against: The interactions involved in left quadrant where the bond angles characteristic of the protein folding are very complex, so the synthetic protein will conformation are concentrated; (b), a series of helices, is most likely fold in another form. Model 3: It would fold to described by plot (d), where most of the allowable something else. For: The interactions involved in protein conformations are in the lower left quadrant. folding are very complex, so the synthetic protein will most 11. The bacterial enzyme is a collagenase; it destroys the connective likely fold in another form. Against: Because the individual tissue barrier of the host, allowing the bacterium to invade the components are mirror images of those in the biological tissues. Bacteria do not contain collagen. protein, it will fold in the mirror-image shape. (e) Model 1. The enzyme is active, but with the enantiomeric form of the 12. (a) The number of moles of DNP-valine formed per mole of biological substrate, and it is inhibited by the enantiomeric protein equals the number of amino termini and thus the form of the biological inhibitor. This is consistent with the number of polypeptide chains. (b) 4 (c) Different chains would D-protease being the mirror image of the L-protease. (f) Evans probably run as discrete bands on an SDS polyacrylamide gel. blue is achiral; it binds to both forms of the enzyme. (g) No. 13. (a); it has more amino acid residues that favor -helical Because proteases contain only L-amino acids and recognize structure (see Table 4–1). only L-peptides, chymotrypsin would not digest the D-protease. 14. (a) Aromatic residues seem to play an important role in (h) Not necessarily. Depending on the individual enzyme, any stabilizing amyloid fibrils. Thus, molecules with aromatic of the problems listed in (b) could result in an inactive enzyme. substituents may inhibit amyloid formation by interfering with the stacking or association of the aromatic side chains. Chapter 5 (b) Amyloid is formed in the pancreas in association with type 2 1. Protein B has a higher affinity for ligand X; it will be half- diabetes, as it is in the brain in Alzheimer disease. Although the saturated at a much lower concentration of X than will protein 6 Ϫ1 9 Ϫ1 amyloid fibrils in the two diseases involve different proteins, the A. Protein A has Ka 5 10 M ; protein B has Ka 5 10 M . fundamental structure of the amyloid is similar and similarly 2. (a), (b), and (c) all have nH , 1.0. Apparent negative stabilized in both, and so they are potential targets for similar cooperativity in ligand binding can be caused by the presence of drugs designed to disrupt this structure. two or more types of ligand-binding sites with different affinities 15. (a) NFB transcription factor, also called RelA transforming for the ligand on the same or different proteins in the same factor. (b) No. You will obtain similar results, but with solution. Apparent negative cooperativity is also commonly additional related proteins listed. (c) The protein has two observed in heterogeneous protein preparations. There are few subunits. There are multiple variants of the subunits, with the well-documented cases of true negative cooperativity. best characterized being 50, 52, or 65 kDa. These pair with each 3. (a) decreases (b) increases (c) decreases (d) increases other to form a variety of homodimers and heterodimers. The 25 21 4. kd 5 8.9 3 10 s . structures of a number of different variants can be found in the 5. (a) 0.5 nM (shortcut: the K is equivalent to the ligand PDB. (d) The NFB transcription factor is a dimeric protein d concentration where 5 0.5). (b) Protein 2 has the highest that binds specific DNA sequences, enhancing transcription of affinity, as it has the lowest K . nearby genes. One such gene is the immunoglobulin light d chain, from which the transcription factor gets its name. 6. The cooperative behavior of hemoglobin arises from subunit interactions. 16. (a) Aba is a suitable replacement because Aba and Cys have side chains of approximately the same size and are similarly 7. (a) The observation that hemoglobin A (HbA; maternal) is hydrophobic. However, Aba cannot form disulfide bonds, so it about 60% saturated when the pO2 is 4 kPa, whereas will not be a suitable replacement if these are required. hemoglobin F (HbF; fetal) is more than 90% saturated under (b) There are many important differences between the the same physiological conditions, indicates that HbF has a synthesized protein and HIV protease produced by a human higher O2 affinity than HbA. (b) The higher O2 affinity of HbF cell, any of which could result in an inactive synthetic enzyme: ensures that oxygen will flow from maternal blood to fetal blood (1) Although Aba and Cys have similar size and in the placenta. Fetal blood approaches full saturation where hydrophobicity, Aba may not be similar enough for the protein the O2 affinity of HbA is low. (c) The observation that the to fold properly. (2) HIV protease may require disulfide bonds O2-saturation curve of HbA undergoes a larger shift on BPG for proper functioning. (3) Many proteins synthesized by binding than that of HbF suggests that HbA binds BPG more ribosomes fold as they are produced; the protein in this study tightly than does HbF. Differential binding of BPG to the two folded only after the chain was complete. (4) Proteins hemoglobins may determine the difference in their O2 affinities. synthesized by ribosomes may interact with the ribosomes as 8. (a) Hb Memphis (b) HbS, Hb Milwaukee, Hb Providence, they fold; this is not possible for the protein in the study. possibly Hb Cowtown (c) Hb Providence (5) Cytosol is a more complex solution than the buffer used in 9. More tightly. An inability to form tetramers would limit the the study; some proteins may require specific, unknown cooperativity of these variants, and the binding curve would proteins for proper folding. (6) Proteins synthesized in cells become more hyperbolic. Also, the BPG-binding site would be AbbreviatedSolutionsToProblems.indd Page AS-6 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-6 Abbreviated Solutions to Problems

disrupted. Oxygen binding would probably be tighter, because would block actin binding and prevent movement. An antibody that the default state in the absence of bound BPG is the tight- bound to actin would also prevent actin-myosin interaction and binding R state. thus movement. (d) There are two possible explanations: (1) Ϫ8 Ϫ8 Ϫ8 10. (a) 1 3 10 M (b) 5 3 10 M (c) 8 3 10 M Trypsin cleaves only at Lys and Arg residues (see Table 3–6) so Ϫ7 (d) 2 3 10 M. Note that a rearrangement of Eqn 5–8 would not cleave at many sites in the protein. (2) Not all Arg or Lys residues are equally accessible to trypsin; the most-exposed sites gives [L] 5 Kd /(1 2 ). 11. The epitope is likely to be a structure that is buried when would be cleaved first. (e) The S1 model. The hinge model G-actin polymerizes to F-actin. predicts that bead-antibody-HMM complexes (with the hinge) would move, but bead-antibody-SHMM complexes (no hinge) 12. Many pathogens, including HIV, have mechanisms by which would not. The S1 model predicts that because both complexes they can repeatedly alter the surface proteins to which include S1, both would move. The finding that the beads move with immune system components initially bind. Thus the host SHMM (no hinge) is consistent only with the S1 model. (f) With organism regularly faces new antigens and requires time to fewer myosin molecules bound, the beads could temporarily fall off mount an immune response to each one. As the immune the actin as a myosin let go of it. The beads would then move more system responds to one variant, new variants are created. slowly, as time is required for a second myosin to bind. At higher 13. Binding of ATP to myosin triggers dissociation of myosin from myosin density, as one myosin lets go, another quickly binds, the actin thin filament. In the absence of ATP, actin and myosin leading to faster motion. (g) Above a certain density, what limits bind tightly to each other. the rate of movement is the intrinsic speed with which myosin 14. molecules move the beads. The myosin molecules are moving at a maximum rate and adding more will not increase speed. (h) Because the force is produced in the S1 head, damaging the S1 head would probably inactivate the resulting molecule, and SHMM would be incapable of producing movement. (i) The S1 head must be held together by noncovalent interactions that are strong (a) (b) (c) (d) enough to retain the active shape of the molecule.

15. (a) Chain L is the light chain and chain H is the heavy chain of the Fab fragment of this antibody molecule. Chain Y is Chapter 6 lysozyme. (b) structures are predominant in the variable 1. The activity of the enzyme that converts sugar to starch is and constant regions of the fragment. (c) Fab heavy-chain destroyed by heat denaturation. Ϫ6 fragment, 218 amino acid residues; light-chain fragment, 214; 2. 2.4 3 10 M lysozyme, 129. Less than 15% of the lysozyme molecule is in 3. 9.5 3 108 years contact with the Fab fragment. (d) In the H chain, residues 4. The enzyme-substrate complex is more stable than the enzyme that seem to be in contact with lysozyme include Gly31, Tyr32, alone. Arg99, Asp100, and Tyr101. In the L chain the residues that seem to be in contact with lysozyme include Tyr32, Tyr49, Tyr50, and 5. (a) 190 Å (b) Three-dimensional folding of the enzyme brings Trp92. In lysozyme, residues Asn19, Gly22, Tyr23, Ser24, Lys116, the amino acid residues into proximity. Gly117, Thr118, Asp119, Gln121, and Arg125 seem to be situated at 6. The reaction rate can be measured by following the decrease in the antigen-antibody interface. Not all these residues are absorption by NADH (at 340 nm) as the reaction proceeds. adjacent in the primary structure. Folding of the polypeptide Determine the Km value; using substrate concentrations well chain into higher levels of structure brings the nonconsecutive above the Km, measure initial rate (rate of NADH disappearance residues together to form the antigen-binding site. with time, measured spectrophotometrically) at several known enzyme concentrations, and make a plot of initial rate versus 16. (a) The protein with a K of 5 M will have the highest affinity for d concentration of enzyme. The plot should be linear, with a slope ligand L. When the K is 10 M, doubling [L] from 0.2 to 0.4 M d that provides a measure of LDH concentration. (values well below the Kd) will nearly double (the actual increase factor is 1.96). This is a property of the hyperbolic curve; 7. (b), (e), (g) Ϫ3 at low ligand concentrations, is an almost linear function of [L]. 8. (a) 1.7 3 10 M (b) 0.33; 0.67; 0.91 (c) The upper curve

On the other hand, doubling [L] from 40 to 80 M (well above the corresponds to enzyme B ([X] . Km for this enzyme); the lower Kd, where the binding curve is approaching its asymptotic limit) curve, enzyme A. Ϫ1 will increase by a factor of only 1.1. The increase factors are 9. (a) 400 s (b) 10 M (c) 5 2, 9 5 3 (d) Mixed inhibitor identical for the curves generated from Eqn 5–11. (b) 5 0.998. 10. (a) 24 nM (b) 4 M (V is exactly half V , so [A] 5 K ) (c) A variety of answers will be obtained, depending on the 0 max m (c) 40 M (V0 is exactly half Vmax, so [A] 5 10 times Km in the values entered for the different parameters. Ϫ1 Ϫ6 presence of inhibitor) (d) No. kcat/Km 5 (0.33 s )/(4 3 10 M) 4 Ϫ1 Ϫ1 17. (a) Myosin 5 8.25 3 10 M s , well below the diffusion-controlled limit. Ϫ5 11. Vmax 140 M/min; Km 1 3 10 M Antibody 12. (a) Vmax 5 51.5 mM/min; Km 5 0.59 mM (b) Competitive inhibition Protein A Bacterial cell 13. Km 5 2.2 mM; Vmax 5 0.50 mol/min 14. Curve A 7 Ϫ1 15. kcat 5 2.0 3 10 min 16. The basic assumptions of the Michaelis-Menten equation still hold. The reaction is at steady state, and the rate is determined

by V0 5 k2 [ES]. The equations needed to solve for [ES] are [E][I] [Et] 5 [E] 1 [ES] 1 [EI] and [EI] 5 The drawing is not to scale; any given cell would have many more KI myosin molecules on its surface. (b) ATP is needed to provide the [E] can be obtained by rearranging Eqn 6–19. The rest follows the chemical energy to drive the motion (see Chapter 13). (c) An pattern of the Michaelis-Menten equation derivation in the text.

antibody that bound to the myosin tail, the actin-binding site, 17. Minimum Mr 5 29,000 AbbreviatedSolutionsToProblems.indd Page AS-7 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-7

18. Activity of the prostate enzyme equals total phosphatase activity Chapter 7 in a blood sample minus phosphatase activity in the presence of 1. With reduction of the carbonyl oxygen to a hydroxyl group, the enough tartrate to completely inhibit the prostate enzyme. chemistry at C-1 and C-3 is the same; the glycerol molecule is 19. The inhibition is mixed. Because Km seems not to change not chiral. appreciably, this could be the special case of mixed inhibition 2. Epimers differ by the configuration about only one carbon. called noncompetitive. (a) D-altrose (C-2), D-glucose (C-3), D-gulose (C-4) 20. The [S] at which V0 5 Vmax/2 9 is obtained when all terms except (b) D-idose (C-2), D-galactose (C-3), D-allose (C-4) Vmax on the right side of Eqn 6–30—that is, [S]/( Km 1 9[S])— (c) D-arabinose (C-2), D-xylose (C-3) 1 ¿ ¿ 1 ¿ equal /2 . Begin with [S]/( Km 1 [S]) 5 /2 and solve for [S]. 3. Osazone formation destroys the configuration around C-2 of 35 21. The optimum activity occurs when Glu is protonated and aldoses, so aldoses differing only at the C-2 configuration give 52 Asp is unprotonated. the same derivative, with the same melting point. Ϫ1 22. (a) Increase factor 5 1.96; V0 5 50 M s ; increase factor 5 1.048. 4. To convert -D-glucose to -D-glucose, the bond between C-1 (b) When 5 2.0, the curve is shifted to the right as the Km is and the hydroxyl on C-5 (as in Fig. 7–6). To convert D-glucose to increased by a factor of 2. When 9 5 3.0, the asymptote of the D-mannose, either the OH or the OOH on C-2. Conversion curve (the Vmax) declines by a factor of 3. When 5 2.0 and between chair conformations does not require bond breakage; this 9 5 3.0, the curve briefly rises above the curve where both is the critical distinction between configuration and conformation. and 9 5 1.0, due to a decline in Km. However, the asymptote 5. No; glucose and galactose differ at C-4. is lower, because V declines by a factor of 3. (c) When max 6. (a) Both are polymers of D-glucose, but they differ in the 5 2.0, the x intercept moves to the right. When 5 2.0 and glycosidic linkage: (1S4) for cellulose, (1S4) for glycogen. 9 5 3.0, the x intercept moves to the left. (b) Both are hexoses, but glucose is an aldohexose, fructose a 23. (a) In the wild-type enzyme, the substrate is held in place by a ketohexose. (c) Both are disaccharides, but maltose has two hydrogen bond and an ion-dipole interaction between the (1S4)-linked D-glucose units; sucrose has (142)-linked 109 charged side chain of Arg and the polar carbonyl of pyruvate. D-glucose and D-fructose. During catalysis, the charged Arg109 side chain also stabilizes the 7. CH OH polarized carbonyl transition state. In the mutant, the binding is 2 reduced to just a hydrogen bond, substrate binding is weaker, O H H and ionic stabilization of the transition state is lost, reducing H catalytic activity. (b) Because Lys and Arg are roughly the same HO H HO O size and have a similar positive charge, they probably have very CH similar properties. Furthermore, because pyruvate binds to 2 171 H OH O Arg by (presumably) an ionic interaction, an Arg to Lys H OH mutation would probably have little effect on substrate binding. H reducing (c) The “forked” arrangement aligns two positively charged HO H2N sugar H groups of Arg residues with the negatively charged oxygens of HO pyruvate and facilitates two combined hydrogen-bond and ion- H H dipole interactions. When Lys is present, only one such combined hydrogen-bond and ion-dipole interaction is possible, thus 8. A hemiacetal is formed when an aldose or ketose condenses reducing the strength of the interaction. The positioning of the with an alcohol; a glycoside is formed when a hemiacetal substrate is less precise. (d) Ile250 interacts hydrophobically with condenses with an alcohol (see Fig. 7–5). the ring of NADH. This type of interaction is not possible with 9. Fructose cyclizes to either the pyranose or the furanose the hydrophilic side chain of Gln. (e) The structure is shown structure. Increasing the temperature shifts the equilibrium in below. (f) The mutant enzyme rejects pyruvate because the direction of the furanose, the less sweet form. pyruvate’s hydrophobic methyl group will not interact with the 10. The rate of mutarotation is sufficiently high that, as the enzyme 102 highly hydrophilic guanidinium group of Arg . The mutant consumes -D-glucose, more -D-glucose is converted to the binds oxaloacetate because of the strong ionic interaction form and, eventually, all the glucose is oxidized. Glucose oxidase between the Arg102 side chain and the carboxyl of oxaloacetate. is specific for glucose and does not detect other reducing sugars (g) The protein must be flexible enough to accommodate the (such as galactose) that react with Fehling’s reagent. added bulk of the side chain and the larger substrate. 11. (a) Measure the change in optical rotation with time. (b) The optical rotation of the mixture is negative (inverted) relative to Arg102 that of the sucrose solution. (c) 22.08 NH 12. Prepare a slurry of sucrose and water for the core; add a small amount of sucrase (invertase); immediately coat with chocolate. C 13. Sucrose has no free anomeric carbon to undergo mutarotation. HN + NH 109 14. Arg H H CH2OH NH Thr246 O O – O H O CH H 2 C C H3C C OH O + HO H H OH HN NH CH H HO H H H H 2 O C Oxalo- H HO H NH acetate N (NADH) H OH HO H His195 + C H N – H OH H O O H CH3 Yes; yes O H H – O HN + NH H3CCHC 2 15. N-Acetyl--D-glucosamine is a reducing sugar; its C-1 can be C C Ile250 oxidized (see p. 252). D-Gluconate is not a reducing sugar; its C-1 is already at the oxidation state of a carboxylic acid. Asp168 NH GlcN(141)Glc is not a reducing sugar; the anomeric carbons Arg171 of both monosaccharides are involved in the glycosidic bond. AbbreviatedSolutionsToProblems.indd Page AS-8 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-8 Abbreviated Solutions to Problems

16. Humans lack cellulase in the gut and cannot break down cellulose. this will give confusing and perhaps uninterpretable structural 17. Native cellulose consists of glucose units linked by (1S4) results. A qualitative assay would detect the presence of activity, glycosidic bonds, which force the polymer chain into an even if it had become significantly degraded. (d) Results 1 and 2. extended conformation. Parallel series of these extended chains Result 1 is consistent with the known structure, because type B form intermolecular hydrogen bonds, aggregating into long, antigen has three molecules of galactose; types A and O each have tough, insoluble fibers. Glycogen consists of glucose units linked only two. Result 2 is also consistent, because type A has two amino by (1S4) glycosidic bonds, which cause bends in the chain sugars (N-acetylgalactosamine and N-acetylglucosamine); types B and prevent formation of long fibers. In addition, glycogen is and O have only one (N-acetylglucosamine). Result 3 is not highly branched and, because many of its hydroxyl groups are consistent with the known structure: for type A, the glucosamine: exposed to water, is highly hydrated and disperses in water. galactosamine ratio is 1:1; for type B, it is 1:0. (e) The samples Cellulose is a structural material in plants, consistent with were probably impure and/or partly degraded. The first two results its side-by-side aggregation into insoluble fibers. Glycogen is a were correct possibly because the method was only roughly storage fuel in animals. Highly hydrated glycogen granules with quantitative and thus not as sensitive to inaccuracies in their many nonreducing ends are rapidly hydrolyzed by glycogen measurement. The third result is more quantitative and thus more phosphorylase to release glucose 1-phosphate. likely to differ from predicted values because of impure or 18. Cellulose is several times longer; it assumes an extended degraded samples. (f) An exoglycosidase. If it were an conformation, whereas amylose has a helical structure. endoglycosidase, one of the products of its action on O antigen would include galactose, N-acetylglucosamine, or 19. 6,000 residues/s N-acetylgalactosamine, and at least one of those sugars would be 20. 11 s able to inhibit the degradation. Given that the enzyme is not 21. The ball-and-stick model of the disaccharide in Fig. 7–18b shows inhibited by any of these sugars, it must be an exoglycosidase, no steric interactions, but a space-filling model, showing atoms removing only the terminal sugar from the chain. The terminal with their real relative sizes, would show several strong steric sugar of O antigen is fucose, so fucose is the only sugar that could hindrances in the 21708, 21708 conformer that are not present inhibit the degradation of O antigen. (g) The exoglycosidase in the 308, 2408 conformer. removes N-acetylgalactosamine from A antigen and galactose from 22. The negative charges on chondroitin sulfate repel each other B antigen. Because fucose is not a product of either reaction, it will and force the molecule into an extended conformation. The not prevent removal of these sugars, and the resulting substances polar molecule attracts many water molecules, increasing the will no longer be active as A or B antigen. However, the products molecular volume. In the dehydrated solid, each negative charge should be active as O antigen, because degradation stops at fucose. is counterbalanced by a positive ion, and the molecule (h) All the results are consistent with Fig. 10–15. (1) D-Fucose and condenses. L-galactose, which would protect against degradation, are not 23. Positively charged amino acid residues would bind the highly present in any of the antigens. (2) The terminal sugar of A antigen negatively charged groups on heparin. In fact, Lys residues of is N-acetylgalactosamine, and this sugar alone protects this antigen antithrombin III interact with heparin. from degradation. (3) The terminal sugar of B antigen is galactose, 24. 8 possible sequences, 144 possible linkages, and 64 which is the only sugar capable of protecting this antigen. stereochemical possibilities, for a total of 73,728 permutations! Chapter 8 25. 1. N-3 and N-7 Oligosaccharide 2. (59)GCGCAATATTTTGAGAAATATTGCGC(39); it contains a chains: palindrome. The individual strands can form hairpin structures; 0 the two strands can form a cruciform. 1 3. 9.4 3 10Ϫ4 g 2

Electrophoresis 4. (a) 408 (b) 08 3 5. The RNA helix is in the A conformation; the DNA helix is + generally in the B conformation. 26. Oligosaccharides; their subunits can be combined in more ways 6. In eukaryotic DNA, about 5% of C residues are methylated. than the amino acid subunits of oligopeptides. Each hydroxyl 5-Methylcytosine can spontaneously deaminate to form thymine; group can participate in glycosidic bonds, and the configuration the resulting G–T pair is one of the most common mismatches in of each glycosidic bond can be either or . The polymer can eukaryotic cells. be linear or branched. 7. Higher 27. (a) Branch-point residues yield 2,3-di-O-methylglucose; the 8. Without the base, the ribose ring can be opened to generate the unbranched residues yield 2,3,6-tri-O-methylglucose. (b) 3.75% noncyclic aldehyde form. This, and the loss of base-stacking 28. Chains of (1S6)-linked D-glucose residues with occasional interactions, could contribute significant flexibility to the DNA (1S3)-linked branches, with about one branch every 20 residues backbone. 29. (a) The tests involve trying to dissolve only part of the sample in a 9. CGCGCGTGCGCGCGCG variety of solvents, then analyzing both dissolved and undissolved 10. Base stacking in nucleic acids tends to reduce the absorption of materials to see whether their compositions differ. (b) For a pure UV light. Denaturation involves loss of base stacking, and UV substance, all molecules are the same and any dissolved fraction absorption increases. will have the same composition as any undissolved fraction. An 11. 0.35 mg/mL impure substance is a mixture of more than one compound. When treated with a particular solvent, more of one component may 12. O dissolve, leaving more of the other component(s) behind. As a HOCH2 O OH result, the dissolved and undissolved fractions have different C N O compositions. (c) A quantitative assay allows researchers to be H H HN C sure that none of the activity has been lost through degradation. H H CH OOP CC When determining the structure of a molecule, it is important that H N N N the sample under analysis consist only of intact (undegraded) HO H 2 H OH molecules. If the sample is contaminated with degraded material, Deoxyribose Guanine Phosphate AbbreviatedSolutionsToProblems.indd Page AS-9 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-9

Solubilities: phosphate . deoxyribose . guanine. The highly the A:G and T:C ratios. G 5 C: Again, the G:C ratio is very close polar phosphate groups and sugar moieties are on the outside of to 1, and the other ratios vary widely. (A 1 G) 5 (T 1 C): This the double helix, exposed to water; the hydrophobic bases are in is the purine:pyrimidine ratio, which also is very close to 1. the interior of the helix. (e) The different “core” fractions represent different regions of 13. If dCTP is omitted, when the first G residue is encountered in the wheat germ DNA. If the DNA were a monotonous repeating the template, ddCTP will be added, and polymerization will halt. sequence, the base composition of all regions would be the Only one band will be seen in the sequencing gel. same. Because different core regions have different sequences, the DNA sequence must be more complex. 14. 1234 Chapter 9 1. (a) (59) – – – G(39) and (59)AATTC – – – (39) (39) – – – CTTAA(59) (39)G – – – (59) (b) (59) – – – GAATT(39) and (59)AATTC – – – (39) (39) – – – CTTAA(59) (39)TTAAG – – – (59) (c) (59) – – – GAATTAATTC – – – (39) (39) – – – CTTAATTAAG – – – (59) Electrophoresis (d) (59) – – – G(39) and (59)C – – – (39) (39) – – – C(59) (39)G – – – (59) (e) (59) – – – GAATTC – – – (39) (39) – – – CTTAAG – – – (59) 15. (59)POGCGCCAUUGC(39)OOH (f) (59) – – – CAG(39) and (59)CTG – – – (39) (59)POGCGCCAUUG(39)OOH (39) – – – GTC(59) (39)GAC – – – (59) (59)POGCGCCAUU(39)OOH (g) (59) – – – CAGAATTC – – – (39) (59)POGCGCCAU(39)OOH (39) – – – GTCTTAAG – – – (59) (59)POGCGCCA(39)OOH (h) Method 1: Cut the DNA with EcoRI as in (a). At this point, (59)POGCGCC(39)OOH one could treat the DNA as in (b) or (d), then ligate a synthetic (59)POGCGC(39)OOH DNA fragment with the BamHI recognition sequence between (59)POGCG(39)OOH the two resulting blunt ends. Method 2 (more efficient): (59)POGC(39)OOH Synthesize a DNA fragment with the structure and the nucleoside 59-phosphates (59)AATTGGATCC(39) 16. (a) Water is a participant in most biological reactions, (39)CCTAGGTTAA(59) including those that cause mutations. The low water content This would ligate efficiently to the sticky ends generated by in endospores reduces the activity of mutation-causing EcoRI cleavage, would introduce a BamHI site, but would not enzymes and slows the rate of nonenzymatic depurination regenerate the EcoRI site. (i) The four fragments (with N 5 any reactions, which are hydrolysis reactions. (b) UV light nucleotide), in order of discussion in the problem, are induces formation of cyclobutane pyrimidine dimers. Because (59)AATTCNNNNCTGCA(39) B. subtilis is a soil organism, spores can be lofted to the top (39)GNNNNG(59) of the soil or into the air, where they may be subject to (59)AATTCNNNNGTGCA(39) prolonged UV exposure. (39)GNNNNC(59) 17. DMT is a blocking group that prevents reaction of the incoming (59)AATTGNNNNCTGCA(39) base with itself. (39)CNNNNG(59) 18. (a) Right-handed. The base at one 59 end is adenine; at the (59)AATTGNNNNGTGCA(39) other 59 end, cytidine. (b) Left-handed (c) If you cannot see (39)CNNNNC(59) the structures in stereo, see additional tips in the expanded 2. phage DNA can be packaged into infectious phage particles solutions manual, or use a search engine to find tips online. only if it is between 40,000 and 53,000 bp in length. Since 19. (a) It would not be easy! The data for different samples from bacteriophage vectors generally include about 30,000 bp (in two the same organism show significant variation, and the recovery pieces), they will not be packaged into phage particles unless is never 100%. The numbers for C and T show much more they contain a sufficient length of inserted DNA (10,000 to consistency than those for A and G, so for C and T it is much 23,000 bp). easier to make the case that samples from the same organism 3. (a) Plasmids in which the original pBR322 was regenerated have the same composition. But even with the less consistent without insertion of a foreign DNA fragment; these would retain values for A and G, (1) the range of values for different tissues resistance to ampicillin. Also, two or more molecules of pBR322 does overlap substantially; (2) the difference between different might be ligated together with or without insertion of foreign preparations of the same tissue is about the same as the DNA. (b) The clones in lanes 1 and 2 each have one DNA difference between samples from different tissues; and (3) in fragment inserted in different orientations. The clone in lane 3 samples for which recovery is high, the numbers are more has two DNA fragments, ligated such that the EcoRI proximal consistent. (b) This technique would not be sensitive enough to ends are joined. detect a difference between normal and cancerous cells. Cancer is caused by mutations, but these changes in DNA—a few base 4. (59)GAAAGTCCGCGTTATAGGCATG(39) pairs out of several billion—would be too small to detect with (39)ACGTCTTTCAGGCGCAATATCCGTACTTAA(59) these techniques. (c) The ratios of A:G and T:C vary widely 5. Your test would require DNA primers, a heat-stable DNA among different species. For example, in the bacterium Serratia polymerase, deoxynucleoside triphosphates, and a PCR marcescens, both ratios are 0.4, meaning that the DNA contains machine (thermal cycler). The primers would be designed to mostly G and C. In Haemophilus influenzae, by contrast, the amplify a DNA segment encompassing the CAG repeat. The ratios are 1.74 and 1.54, meaning that the DNA is mostly A and DNA strand shown is the coding strand, oriented 59S39 left to T. (d) Conclusion 4 has three requirements. A 5 T: The table right. The primer targeted to DNA to the left of the repeat shows an A:T ratio very close to 1 in all cases. Certainly, the would be identical to any 25-nucleotide sequence shown in the variation in this ratio is substantially less than the variation in region to the left of the CAG repeat. The primer on the right AbbreviatedSolutionsToProblems.indd Page AS-10 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-10 Abbreviated Solutions to Problems

side must be complementary and antiparallel to a 13. The primers can be used to probe libraries containing long 25-nucleotide sequence to the right of the CAG repeat. Using genomic clones to identify contig ends that lie close to each the primers, DNA including the CAG repeat would be amplified other. If the contigs flanking the gap are close enough, the by PCR, and its size would be determined by comparison to size primers can be used in PCR to directly amplify the intervening markers after electrophoresis. The length of the DNA would DNA separating the contigs, which can then be cloned and reflect the length of the CAG repeat, providing a simple test for sequenced. the disease. 14. ATSAAGWDEWEGGKVLIHLDGKLQNRGALLELDIGAV 6. Design PCR primers that are complementary to the DNA in the 15. The same disease condition can be caused by defects in two or deleted segment but that would direct DNA synthesis away from more genes, which are on different chromosomes. each other. No PCR product will be generated unless the ends 16. (a) DNA solutions are highly viscous because the very long of the deleted segment are joined to create a circle. molecules are tangled in solution. Shorter molecules tend to 7. The plant expressing firefly luciferase must take up luciferin, tangle less and form a less viscous solution, so decreased the substrate of luciferase, before it can “glow” (albeit weakly). viscosity corresponds to shortening of the polymers—as caused The plant expressing green fluorescent protein glows without by nuclease activity. (b) An endonuclease. An exonuclease requiring any other compound. removes single nucleotides from the 59 or 39 end and would 8. Primer 1: CCTCGAGTCAATCGATGCTG produce TCA-soluble 32P-labeled nucleotides. An endonuclease Primer 2: CGCGCACATCAGACGAACCA cuts DNA into oligonucleotide fragments and produces little or Recall that all DNA sequences are always written in the 59 to 39 no TCA-soluble 32P-labeled material. (c) The 59 end. If the direction, left to right; that the two strands of a DNA molecule phosphate were left on the 39 end, the kinase would incorporate are antiparallel; and that both PCR primers must target the end significant 32P as it added phosphate to the 59 end; treatment sequences so that their 39 ends are oriented toward the with the phosphatase would have no effect on this. In this case, segment to be amplified. In a lab, writing a sequence in the samples A and B would incorporate significant amounts of 32P. wrong orientation on an order form when ordering a synthetic When the phosphate is left on the 59 end, the kinase does not oligonucleotide primer can be a very expensive mistake. incorporate any 32P: it cannot add a phosphate if one is already 9. 91 5 374 2 68 present. Treatment with the phosphatase removes 59 phosphate, and the kinase then incorporates significant amounts of 32P. Sample A will have little or no 32P, and B will A show substantial 32P incorporation—as was observed. B (d) Random breaks would produce a distribution of fragments C of random size. The production of specific fragments indicates that the enzyme is site-specific. (e) Cleavage at the site of D recognition. This produces a specific sequence at the 59 end of E the fragments. If cleavage occurred near but not within the recognition site, the sequence at the 59 end of the fragments F would be random. (f) The results are consistent with two 10. The production of labeled antibodies is difficult and expensive. recognition sequences, as shown below, cleaved where shown The labeling of every antibody to every protein target would be by the arrows, impractical. By labeling one antibody preparation for binding to all antibodies of a particular class, the same labeled antibody (5Ј) – – – GTT AAC – – – (3Ј) preparation can be used in many different immunofluorescence (3Ј) – – – CAA TTG – – – (5Ј) experiments. 11. Express the protein in yeast strain 1 as a fusion protein with one of the domains of Gal4p—say, the DNA-binding domain. Using which gives the (59)pApApC and (39)TpTp fragments, and yeast strain 2, make a library in which essentially every protein of the fungus is expressed as a fusion protein with the interaction (5Ј) – – – GTC GAC – – – (3Ј) domain of Gal4p. Mate strain 1 with the strain 2 library, and look (3Ј) – – – CAG CTG – – – (5Ј) for colonies that are colored due to expression of the reporter gene. These colonies will generally arise from mated cells containing a fusion protein that interacts with your target protein. which gives the (59)pGpApC and (39)CpTp fragments 12. Cover spot 4, add solution containing activated T, irradiate, wash.

1. A–T 2. G–T 3. A–T 4. G–C Chapter 10 Cover spots 2 and 4, add solution containing activated G, irradi- 1. The term “lipid” does not specify a particular chemical ate, wash. structure. Compounds are categorized as lipids based on their greater solubility in organic solvents than in water. 1. A–T–G 2. G–T 3. A–T–G 4. G–C 2. (a) The number of cis double bonds. Each cis double bond Cover spot 3, add solution containing activated C, irradiate, causes a bend in the hydrocarbon chain, lowering the melting wash. temperature. (b) Six different triacylglycerols can be constructed, in order of increasing melting points: 1. A–T–G–C 2. G–T–C 3. A–T–G 4. G–C–C OOO , OOP 5 OPO , PPO 5 POP , PPP Cover spots 1, 3, and 4, add solution containing activated C, irradiate, wash. where O 5 oleic and P 5 palmitic acid. The greater the content of saturated fatty acid, the higher is the melting point. 1. A–T–G–C 2. G–T–C–C 3. A–T–G 4. G–C–C (c) Branched-chain fatty acids increase the fluidity of membranes because they decrease the extent of membrane lipid Cover spots 1 and 2, add solution containing activated G, irradi- packing. ate, wash. 3. Lecithin, an amphipathic compound, is an emulsifying agent, 1. A–T–G–C 2. G–T–C–C 3. A–T–G–C 4. G–C–C–C facilitating the solubilization of butter. AbbreviatedSolutionsToProblems.indd Page AS-11 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-11

4. 16. Diacylglycerol is hydrophobic and remains in the membrane. Inositol 1,4,5-trisphosphate is highly polar, very soluble in water, and more readily diffusible in the cytosol. Both are second messengers. 17. Water-soluble vitamins are more rapidly excreted in the urine and are not stored effectively. Fat-soluble vitamins have very low solubility in water and are stored in body lipids. 18. (a) Glycerol and the sodium salts of palmitic and stearic acids. (b) D-Glycerol 3-phosphocholine and the sodium salts of palmitic and oleic acids. Squalene 19. Solubilities in water: monoacylglycerol . diacylglycerol . 5. Spearmint is (R)-carvone; caraway is (S)-carvone. triacylglycerol. 6. COOH COOH 20. First eluted to last eluted: cholesteryl palmitate and ϩ ϩ triacylglycerol; cholesterol and n-tetradecanol; CH NH H N C H 3 3 phosphatidylcholine and phosphatidylethanolamine; sphingomyelin; phosphatidylserine and palmitate. CH3 CH3 (R)-2-Aminopropanoic acid (S)-2-Aminopropanoic acid 21. (a) Subject acid hydrolysates of each compound to chromatography (GLC or silica gel TLC) and compare the result with known standards. Sphingomyelin hydrolysate: OH COOH sphingosine, fatty acids, phosphocholine, choline, and phosphate; cerebroside hydrolysate: sphingosine, fatty acids,

H3C C COOH H3C C OH sugars, but no phosphate. (b) Strong alkaline hydrolysis of sphingomyelin yields sphingosine; phosphatidylcholine yields H H glycerol. Detect hydrolysate components on thin-layer (R)-2-Hydroxypropanoic acid (S)-2-Hydroxypropanoic acid chromatograms by comparing with standards or by their differential reaction with FDNB (only sphingosine reacts to form 7. Hydrophobic units: (a) 2 fatty acids; (b), (c), and (d) 1 fatty acid a colored product). Treatment with phospholipase A1 or A2 and the hydrocarbon chain of sphingosine; (e) steroid nucleus and releases free fatty acids from phosphatidylcholine, but not from acyl side chain. Hydrophilic units: (a) phosphoethanolamine; sphingomyelin. (b) phosphocholine; (c) D-galactose; (d) several sugar molecules; 22. Phosphatidylethanolamine and phosphatidylserine. (e) alcohol group (OH) 23. (a) GM1 and globoside. Both glucose and galactose are hexoses, 8. O so “hexose” in the molar ratio refers to glucose 1 galactose. The C ratios for the four gangliosides are: GM1, 1:3:1:1; GM2, 1:2:1:1; O GM3, 1:2:0:1; globoside, 1:3:1:0. (b) Yes. The ratio matches 9. It reduces double bonds, which increases the melting point of GM2, the ganglioside expected to build up in Tay-Sachs disease lipids containing the fatty acids. (see Box 10–1, Fig. 1). (c) This analysis is similar to that used 10. The triacylglycerols of animal fats (grease) are hydrolyzed by by Sanger to determine the amino acid sequence of insulin. The NaOH (saponified) to form soaps, which are much more soluble analysis of each fragment reveals only its composition, not its in water than are triacylglycerols. sequence, but because each fragment is formed by sequential removal of one sugar, we can draw conclusions about sequence. 11. It could only be a sphingolipid (sphingomyelin). The structure of the normal asialoganglioside is ceramide– 12. glucose–galactose–galactosamine–galactose, consistent with Box O O O 10–1 (excluding Neu5Ac, removed before hydrolysis). (d) The H Tay-Sachs asialoganglioside is ceramide–glucose–galactose– OOP O O galactosamine, consistent with Box 10–1. (e) The structure of O O H NH3 the normal asialoganglioside, GM1, is: ceramide–glucose O O O (2 OH involved in glycosidic links; 1 OH involved in ring structure; 3 OOH (2,3,6) free for methylation)–galactose Phosphatidylserine (2 OOH in links; 1 OOH in ring; 3 OOH (2,4,6) free for 13. Long, saturated acyl chains, nearly solid at air temperature, methylation)–galactosamine (2 OOH in links; 1 OOH in ring; form a hydrophobic layer in which a polar compound such as 1 ONH2 instead of an OOH; 2 OOH (4,6) free for O O H2O cannot dissolve or diffuse. methylation)–galactose (1 OH in link; 1 OH in ring; 4 O 14. (a) The free OOH group on C-2 and the phosphocholine head OH (2,3,4,6) free for methylation). (f) Two key pieces of group on C-3 are hydrophilic; the fatty acid on C-1 of information are missing: What are the linkages between the lysolecithin is hydrophobic. (b) Certain steroids such as sugars? Where is Neu5Ac attached?

prednisone inhibit the action of phospholipase A2, inhibiting the release of arachidonic acid from C-2. Arachidonic acid is converted to a variety of eicosanoids, some of which cause Chapter 11

inflammation and pain. (c) Phospholipase A2 releases 1. The area per molecule would be calculated from the known arachidonic acid, a precursor of other eicosanoids with vital amount (number of molecules) of lipid used and the area protective functions in the body; it also breaks down dietary occupied by a monolayer when it begins to resist compression glycerophospholipids. (when the required force increases dramatically, as shown in the 15. The part of the membrane lipid that determines blood type is the plot of force vs. area). oligosaccharide in the head group of the membrane sphingolipids 2. The data support a bilayer of lipid in the dog erythrocytes: a (see Fig. 10–15). This same oligosaccharide is attached to certain single cell, with surface area 98 m2, has a lipid monolayer area membrane glycoproteins, which also serve as points of of 200 m2. In the case of sheep and human erythrocytes, the recognition by the antibodies that distinguish blood groups. data suggest a monolayer, not a bilayer. In fact, significant AbbreviatedSolutionsToProblems.indd Page AS-12 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-12 Abbreviated Solutions to Problems

experimental errors occurred in these early experiments; recent, 22. 8 1 more accurate measurements support a bilayer in all cases. 15 V V 12 L 3. 63 SDS molecules per micelle 4 L 4. (a) Lipids that form bilayers are amphipathic molecules: they V 5 contain a hydrophilic and a hydrophobic region. To minimize the 11 F hydrophobic area exposed to the water surface, these lipids H form two-dimensional sheets, with the hydrophilic regions Q 16 exposed to water and the hydrophobic regions buried in the 18 K interior of the sheet. Furthermore, to avoid exposing the C 9 hydrophobic edges of the sheet to water, lipid bilayers close on N themselves. (b) These sheets form the closed membrane 7 D surfaces that envelop cells and compartments within cells 2 (organelles). T 14 K 5. 2 nm. Two palmitates placed end to end span about 4 nm, R 13 approximately the thickness of a typical bilayer. S 3 T D 6. Decrease. Movement of individual lipids in bilayers occurs much 6 10 17 faster at 37 8C, when the lipids are in the “fluid” phase, than at 108C, when they are in the “solid” phase. The amino acids with the greatest hydropathy index (V, L, F, 7. 35 kJ/mol, neglecting the effects of transmembrane electrical and C) are clustered on one side of the helix. This amphipathic potential; 0.60 mol. helix is likely to dip into the lipid bilayer along its hydrophobic surface while exposing the other surface to the aqueous phase. 8. 13 kJ/mol. Alternatively, a group of helices may cluster with their polar 9. Most of the O2 consumed by a tissue is for oxidative surfaces in contact with one another and their hydrophobic phosphorylation, the source of most of the ATP. Therefore, surfaces facing the lipid bilayer. about two-thirds of the ATP synthesized by the kidney is used 23. 22. To estimate the fraction of membrane surface covered by for pumping Kϩ and Naϩ. ϩ phospholipids, you would need to know (or estimate) the 10. No. The symporter may carry more than one equivalent of Na average cross-sectional area of a phospholipid molecule in a for each mole of glucose transported. bilayer (e.g., from an experiment such as that diagrammed in 11. Salt extraction indicates a peripheral location, and problem 1 in this chapter) and the average cross-sectional area inaccessibility to protease in intact cells indicates an internal of a 50 kDa protein. location. X seems to be a peripheral protein on the cytosolic 24. (a) The rise-per-residue for an helix (Chapter 4) is about 1.5 face of the membrane. Å 5 0.15 nm. To span a 4 nm bilayer, an helix must contain 12. The hydrophobic interactions among membrane lipids are about 27 residues; thus for seven spans, about 190 residues are noncovalent and reversible, allowing membranes to required. A protein of Mr 64,000 has about 580 residues. (b) A spontaneously reseal. hydropathy plot is used to locate transmembrane regions. 13. The temperature of body tissues at the extremities is lower than (c) Because about half of this portion of the epinephrine that of tissues closer to the center of the body. If lipid is to receptor consists of charged residues, it probably represents an remain fluid at this lower temperature, it must contain a higher intracellular loop that connects two adjacent membrane-spanning proportion of unsaturated fatty acids; unsaturated fatty acids regions of the protein. (d) Because this helix is composed lower the melting point of lipid mixtures. mostly of hydrophobic residues, this portion of the receptor is probably one of the membrane-spanning regions of the protein. 14. The energetic cost of moving the highly polar, sometimes charged, head group through the hydrophobic interior of the 25. (a) Model A: supported. The two dark lines are either the bilayer is prohibitive. protein layers or the phospholipid heads, and the clear space is either the bilayer or the hydrophobic core, respectively. Model B: 15. At pH 7, tryptophan bears a positive and a negative charge, but not supported. This model requires a more-or-less uniformly indole is uncharged. The movement of the less polar indole stained band surrounding the cell. Model C: supported, with one through the hydrophobic core of the bilayer is energetically reservation. The two dark lines are the phospholipid heads; the more favorable. clear zone is the tails. This assumes that the membrane proteins Ϫ2 16. 3 3 10 s are not visible, because they do not stain with osmium or do not 17. Treat a suspension of cells with unlabeled NEM in the presence happen to be in the sections viewed. (b) Model A: supported. A of excess lactose, remove the lactose, then add radiolabeled “naked” bilayer (4.5 nm) 1 two layers of protein (2 nm) sums to

NEM. Use SDS-PAGE to determine the Mr of the radiolabeled 6.5 nm, which is within the observed range of thickness. Model band (the transporter). B: neither. This model makes no predictions about membrane 18. Construct a hydropathy plot; hydrophobic regions of 20 or more thickness. Model C: unclear. The result is hard to reconcile with residues suggest transmembrane segments. Determine whether this model, which predicts a membrane as thick as, or slightly the protein in intact erythrocytes reacts with a membrane- thicker than (due to the projecting ends of embedded proteins), impermeant reagent specific for primary amines; if so, the a “naked” bilayer. The model is supported only if the smallest transporter is of type I. values for membrane thickness are correct or if a substantial amount of protein projects from the bilayer. (c) Model A: 19. The leucine transporter is specific for the L isomer, but the unclear. The result is hard to reconcile with this model. If the binding site can accommodate either L-leucine or L-valine. proteins are bound to the membrane by ionic interactions, the Reduction of V in the absence of Naϩ indicates that leucine max model predicts that the proteins contain a high proportion of (or valine) is transported by symport with Naϩ. charged amino acids, in contrast to what was observed. Also, 20. Vmax reduced; Kt unaffected. because the protein layer must be very thin (see (b)), there 21. 1%; estimated by calculating the surface area of the cell and of would not be much room for a hydrophobic protein core, so 10,000 transporter molecules (using the dimensions of hydrophobic residues would be exposed to the solvent. Model B: hemoglobin (5.5 nm diameter, p. 163) as a model globular supported. The proteins have a mixture of hydrophobic residues protein). (interacting with lipids) and charged residues (interacting with AbbreviatedSolutionsToProblems.indd Page AS-13 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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water). Model C: supported. The proteins have a mixture of 9. Amplification results as one molecule of a catalyst activates hydrophobic residues (anchoring in the membrane) and charged many molecules of another catalyst, in an amplification cascade residues (interacting with water). (d) Model A: unclear. The involving, in order, insulin receptor, IRS-1, Raf, MEK, ERK; ERK result is hard to reconcile with this model, which predicts a ratio activates a transcription factor, which stimulates mRNA of exactly 2.0; this would be hard to achieve under physiologically production. relevant pressures. Model B: neither. This model makes no 10. A mutation in ras that inactivates the Ras GTPase activity predictions about amount of lipid in the membrane. Model C: creates a protein that, once activated by the binding of GTP, supported. Some membrane surface area is taken up with continues to give, through Raf, the insulin-response signal. proteins, so the ratio would be less than 2.0, as was observed 11. Shared properties of Ras and G : Both bind either GDP or under more physiologically relevant conditions. (e) Model A: s GTP; both are activated by GTP; both, when active, activate a unclear. The model predicts proteins in extended conformations downstream enzyme; both have intrinsic GTPase activity that rather than globular, so supported only if one assumes that shuts them off after a short period of activation. Differences proteins layered on the surfaces include helical segments. between Ras and G : Ras is a small, monomeric protein; G is Model B: supported. The model predicts mostly globular proteins s s heterotrimeric. Functional difference between G and G : G (containing some helical segments). Model C: supported. The s i s activates adenylyl cyclase, G inhibits it. model predicts mostly globular proteins. (f) Model A: unclear. i The phosphorylamine head groups are protected by the protein 12. Kinase (factor in parentheses): PKA (cAMP); PKG (cGMP); 2ϩ 2ϩ 2ϩ layer, but only if the proteins completely cover the surface will PKC (Ca , DAG); Ca /CaM kinase (Ca , CaM); cyclin- the phospholipids be completely protected from phospholipase. dependent kinase (cyclin); protein Tyr kinase (ligand for the Model B: supported. Most head groups are accessible to receptor, such as insulin); MAPK (Raf); Raf (Ras); glycogen phospholipase. Model C: supported. All head groups are phosphorylase kinase (PKA). accessible to phospholipase. (g) Model A: not supported. 13. Gs remains in its activated form when the nonhydrolyzable Proteins are entirely accessible to trypsin digestion and virtually analog is bound. The analog therefore prolongs the effect of all will undergo multiple cleavage, with no protected hydrophobic epinephrine on the injected cell. segments. Model B: not supported. Virtually all proteins are in 14. (a) Use the -bungarotoxin–bound beads for affinity purification the bilayer and inaccessible to trypsin. Model C: supported. (see Fig. 3–17c) of AChR. Extract proteins from the electric Segments of protein that penetrate or span the bilayer are organs and pass the mixture through the chromatography protected from trypsin; those exposed at the surfaces will be column; the AChR binds selectively to the beads. Elute the AChR cleaved. The trypsin-resistant portions have a high proportion of with a solute that weakens its interaction with -bungarotoxin. hydrophobic residues. (b) Use binding of [125I]-bungarotoxin as a quantitative assay for AChR during purification by various techniques. At each Chapter 12 step, assay AChR by measuring [125I]-bungarotoxin binding 1. X is cAMP; its production is stimulated by epinephrine. to the proteins in the sample. Optimize purification for the (a) Centrifugation sediments adenylyl cyclase (which catalyzes highest specific activity of AChR (counts/min of bound cAMP formation) in the particulate fraction. (b) Added cAMP [125I]-bungarotoxin per mg of protein) in the final material. stimulates glycogen phosphorylase. (c) cAMP is heat stable; it ϩ 15. (a) No. If Vm were set by permeability to (primarily) K , the can be prepared by treating ATP with barium hydroxide. Nernst equation would predict a Vm of 290 mV, not the 2. Unlike cAMP, dibutyryl cAMP passes readily through the plasma observed 295 mV, so some other conductance must contribute

membrane. to Vm. (b) Chloride ion is probably the determinant of Vm; the ϩ 3. (a) It increases [cAMP]. (b) cAMP regulates Na permeability. predicted ECl– is 294 mV.

(c) Replace lost body fluids and electrolytes. 16. (a) Vm of the oocyte membrane changes from 260 mV to 4. (a) The mutation makes R unable to bind and inhibit C, so C is 210 mV—that is, the membrane is depolarized. (b) The effect 2ϩ constantly active. (b) The mutation prevents cAMP binding to R, of KCl depends on influx of Ca from the extracellular medium. leaving C inhibited by bound R. 17. Hyperpolarization results in the closing of voltage-dependent 2ϩ 5. Albuterol raises [cAMP], leading to relaxation and dilation of the Ca channels in the presynaptic region of the rod cell. The 2ϩ bronchi and bronchioles. Because -adrenergic receptors resulting decrease in [Ca ]in diminishes release of an inhibitory control many other processes, this drug would have undesirable neurotransmitter that suppresses activity in the next neuron of side effects. To minimize them, find an agonist specific for the the visual circuit. When this inhibition is removed in response to subtype of -adrenergic receptors found in the bronchial smooth a light stimulus, the circuit becomes active and visual centers in muscle. the brain are excited. ϩ ϩ 6. Hormone degradation; hydrolysis of GTP bound to a G protein; 18. (a) This would prevent influx of Na and Ca2 into the cells in degradation, metabolism, or sequestration of second messenger; response to light; the cone cells would fail to signal the brain receptor desensitization; removal of receptor from the cell surface. that light had been received. Because rod cells are unaffected, the individuals would be able to see but would not have color 7. Fuse CFP to -arrestin and YFP to the cytoplasmic domain of ϩ the -adrenergic receptor, or vice versa. In either case, vision. (b) This would prevent efflux of K , which would lead illuminate at 433 nm and observe at both 476 and 527 nm. If the to depolarization of the -cell membrane and constitutive interaction occurs, emitted light intensity will decrease at release of insulin into the blood. (c) ATP is responsible for 476 nm and increase at 527 nm on addition of epinephrine to closing this channel, so the channels will remain open, cells expressing the fusion proteins. If the interaction does not preventing depolarization of the -cell membrane and release occur, the wavelength of emitted light will remain at 476 nm. of insulin. Some reasons why this might fail: The fusion proteins (1) are 19. Individuals with Oguchi disease might have a defect in inactive or otherwise unable to interact, (2) are not translocated rhodopsin kinase or in arrestin. to their normal subcellular location, or (3) are not stable to 20. Rod cells would no longer show any change in membrane proteolytic breakdown. potential in response to light. This experiment has been done. 2ϩ Ϫ6 8. Vasopressin acts by elevating cytosolic [Ca ] to 10 M, Illumination did activate PDE, but the enzyme could not activating protein kinase C. EGTA injection blocks vasopressin significantly reduce the 8-Br-cGMP level, which remained well action but should not affect the response to glucagon, which above that needed to keep the gated ion channels open. Thus, uses cAMP, not Ca2ϩ, as second messenger. light had no impact on membrane potential. AbbreviatedSolutionsToProblems.indd Page AS-14 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-14 Abbreviated Solutions to Problems

21. (a) On exposure to heat, TRPV1 channels open, causing an (the surroundings) contain complex fuel molecules (a low- influx of Naϩ and Ca2ϩ into the sensory neuron. This depolarizes entropy condition). During incubation, some of these complex

the neuron, triggering an action potential. When the action molecules are converted to large numbers of CO2 and H2O potential reaches the axon terminus, neurotransmitter is molecules (high entropy). This increase in the entropy of the released, signaling the nervous system that heat has been surroundings is larger than the decrease in entropy of the chick sensed. (b) Capsaicin mimics the effects of heat by opening (the system). TRPV1 at low temperature, leading to the false sensation of heat. 2. (a) 24.8 kJ/mol (b) 7.56 kJ/mol (c) 213.7 kJ/mol The extremely low EC50 indicates that even very small amounts 3. (a) 262 (b) 608 (c) 0.30 of capsaicin will have dramatic sensory effects. (c) At low levels, 9 5 D 98 5 2 menthol should open the TRPM8 channel, leading to a sensation 4. Keq 21; G 7.6 kJ/mol of cool; at high levels, both TRPM8 and TRPV3 will open, leading 5. 231 kJ/mol to a mixed sensation of cool and heat, such as you may have 6. (a) 21.68 kJ/mol (b) 24.4 kJ/mol (c) At a given temperature, experienced with very strong peppermints. the value of DG98 for any reaction is fixed and is defined for 22. (a) These mutations might lead to permanent activation of the standard conditions (here, both fructose 6-phosphate and glucose 6-phosphate at 1 M). In contrast, DG is a variable that PGE2 receptor, leading to unregulated cell division and tumor formation. (b) The viral gene might encode a constitutively can be calculated for any set of reactant and product active form of the receptor, causing a constant signal for cell concentrations. division and thus tumor formation. (c) E1A protein might bind 7. K9eq 1; DG98 0 to pRb and prevent E2F from binding, so E2F is constantly 8. Less. The overall equation for ATP hydrolysis can be active and cells divide uncontrollably. (d) Lung cells do not approximated as normally respond to PGE2 because they do not express the 4Ϫ 3Ϫ 2Ϫ ϩ ATP 1 H2O S ADP 1 HPO4 1 H PGE2 receptor; mutations resulting in a constitutively active PGE2 receptor do not affect lung cells. (This is only an approximation, because the ionized species 23. A normal tumor suppressor gene encodes a protein that shown here are the major, but not the only, forms present.) restrains cell division. A mutant form of the protein fails to Under standard conditions (i.e., [ATP] 5 [ADP] 5 [Pi] 5 1 M), suppress cell division, but if either of the two alleles encodes the concentration of water is 55 M and does not change during the reaction. Because Hϩ ions are produced in the reaction, at a normal protein, normal function will continue. A normal ϩ oncogene encodes a regulator protein that triggers cell higher [H ] (pH 5.0) the equilibrium would be shifted to the left division, but only when an appropriate signal (growth factor) is and less free energy would be released. present. The mutant version of the oncogene product 9. 10 constantly sends the signal to divide, whether or not growth 10. 0 factors are present. 24. In a child who develops multiple tumors in both eyes, every Ϫ10 retinal cell had a defective copy of the Rb gene at birth. Early Ϫ20 in the child’s life, several cells independently underwent a second mutation that damaged the one good Rb allele, Ϫ30 producing a tumor. A child who develops a single tumor had,

at birth, two good copies of the Rb gene in every cell; ⌬ G (kJ/mol) Ϫ40 mutation in both Rb alleles in one cell (extremely rare) caused a single tumor. Ϫ50 25. Two cells expressing the same surface receptor may have Ϫ60 different complements of target proteins for protein Ϫ9 Ϫ8 Ϫ7 Ϫ6 Ϫ5 Ϫ4 Ϫ30Ϫ2 Ϫ1 phosphorylation. ln Q 26. (a) The cell-based model, which predicts different receptors present on different cells. (b) This experiment addresses the DG for ATP hydrolysis is lower when [ATP]/[ADP] is low (,,1) issue of the independence of different taste sensations. Even than when [ATP]/[ADP] is high. The energy available to the cell though the receptors for sweet and/or umami are missing, the from a given [ATP] is lower when the [ATP]/[ADP] ratio falls and animals’ other taste sensations are normal; thus, pleasant and greater when it rises. Ϫ3 Ϫ1 Ϫ8 unpleasant taste sensations are independent. (c) Yes. Loss of 11. (a) 3.85 3 10 M ; [glucose 6-phosphate] 5 8.9 3 10 M; no. either T1R1 or T1R3 subunits abolishes umami taste sensation. (b) 14 M; because the maximum solubility of glucose is less than (d) Both models. With either model, removing one receptor 1 M, this is not a reasonable step. (c) 837 (DG98 5 216.7 kJ/mol); Ϫ7 would abolish that taste sensation. (e) Yes. Loss of either the [glucose] 5 1.2 3 10 M; yes. (d) No. This would require

T1R2 or T1R3 subunits almost completely abolishes the sweet such high [Pi] that the phosphate salts of divalent cations taste sensation; complete elimination of sweet taste requires would precipitate. (e) By directly transferring the phosphoryl deletion of both subunits. (f) At very high sucrose group from ATP to glucose, the phosphoryl group transfer concentrations, T1R2 and, to a lesser extent, T1R3 receptors, potential (“tendency” or “pressure”) of ATP is utilized as homodimers, can detect sweet taste. (g) The results are without generating high concentrations of intermediates. The consistent with either model of taste encoding, but do essential part of this transfer is, of course, the enzymatic strengthen the researchers’ conclusions. Ligand binding can be catalysis. completely separated from taste sensation. If the ligand for the 12. (a) 212.5 kJ/mol (b) 214.6 kJ/mol receptor in “sweet-tasting cells” binds a molecule, mice prefer Ϫ 13. (a) 3 3 10 4 (b) 68.7 (c) 7.4 3 104 that molecule as a sweet compound. 14. 213 kJ/mol Chapter 13 15. 46.7 kJ/mol 1. Consider the developing chick as the system; the nutrients, egg 16. Isomerization moves the carbonyl group from C-1 to C-2, setting shell, and outside world are the surroundings. Transformation up a carbon–carbon bond cleavage between C-3 and C-4. Without of the single cell into a chick drastically reduces the entropy of isomerization, bond cleavage would occur between C-2 and C-3, the system. Initially, the parts of the egg outside the embryo generating one two-carbon and one four-carbon compound. AbbreviatedSolutionsToProblems.indd Page AS-15 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-15

17. The mechanism is the same as that of the alcohol subcellular organelle of the oligodendrocyte, either actively dehydrogenase reaction (see Fig. 14–14). pumped at the expense of ATP or drawn in by its attraction to 18. The first step is the reverse of an aldol condensation (see the other molecules in that organelle. aldolase mechanism, Fig. 14–6); the second step is an aldol condensation (see Fig. 13–4). Chapter 14 19. (a) 46 kJ/mol (b) 46 kg; 68% (c) ATP is synthesized as it is 1. Net equation: Glucose 1 2ATP S 2 glyceraldehyde 3-phosphate 1 needed, then broken down to ADP and Pi; its concentration is ϩ maintained in a steady state. 2ADP 1 2H ; DG98 5 2.1 kJ/mol S 20. The ATP system is in a dynamic steady state; [ATP] remains 2. Net equation: 2 Glyceraldehyde 3-phosphate 1 4ADP 1 2Pi ϩ constant because the rate of ATP consumption equals its rate 2 lactate 1 2NAD ; DG98 5 2114 kJ/mol of synthesis. ATP consumption involves release of the 3. GLUT2 (and GLUT1) is found in liver and is always present in terminal () phosphoryl group; synthesis of ATP from ADP the plasma membrane of hepatocytes. GLUT3 is always present involves replacement of this phosphoryl group. Hence the in the plasma membrane of certain brain cells. GLUT4 is terminal phosphate undergoes rapid turnover. In contrast, the normally sequestered in vesicles in cells of muscle and adipose central () phosphate undergoes only relatively slow tissue and enters the plasma membrane only in response to turnover. insulin. Thus, liver and brain can take up glucose from blood 21. (a) 1.7 kJ/mol (b) Inorganic pyrophosphatase catalyzes the regardless of insulin level, but muscle and adipose tissue take up hydrolysis of pyrophosphate and drives the net reaction toward glucose only when insulin levels are elevated in response to high the synthesis of acetyl-CoA. blood glucose. 1 1 4 22. 36 kJ/mol 4. CH3CHO 1 NADH 1 H Δ CH3CH2OH 1 NAD ; Keq¿ 5 1.45 3 10 23. (a) NADϩ/NADH (b) Pyruvate/lactate (c) Lactate formation 5. 28.6 kJ/mol 4 14 14 14 (d) 226.1 kJ/mol (e) 3.63 3 10 6. (a) CH3CH2OH (b) [3- C]glucose or [4- C]glucose 24. (a) 1.14 V (b) 2220 kJ/mol (c) 4 7. Fermentation releases energy, some conserved in the form of 25. (a) 20.35 V (b) 20.320 V (c) 20.29 V ATP but much of it dissipated as heat. Unless the fermenter 26. In order of increasing tendency: (a), (d), (b), (c) contents are cooled, the temperature would become high enough to kill the microorganisms. 27. (c) and (d) 8. Soybeans and wheat contain starch, a polymer of glucose. The 28. (a) The lowest-energy, highest-entropy state occurs when the microorganisms break down starch to glucose, glucose to dye concentration is the same in both cells. If a “fish trap” gap pyruvate via glycolysis, and—because the process is carried out junction allowed unidirectional transport, more of the dye would in the absence of O2 (i.e., it is a fermentation)—pyruvate to end up in the oligodendrocyte and less in the astrocyte. This lactic acid and ethanol. If O2 were present, pyruvate would be would be a higher-energy, lower-entropy state than the starting oxidized to acetyl-CoA, then to CO2 and H2O. Some of the state, violating the second law of thermodynamics. The model acetyl-CoA, however, would also be hydrolyzed to acetic acid proposed by Robinson et al. requires an impossible spontaneous (vinegar) in the presence of oxygen. decrease in entropy. In terms of energy, the model entails a spontaneous change from a lower-energy to a higher-energy 9. C-1. This experiment demonstrates the reversibility of the state without an energy input—again, thermodynamically aldolase reaction. The C-1 of glyceraldehyde 3-phosphate is impossible. (b) Molecules, unlike fish, do not exhibit directed equivalent to C-4 of fructose 1,6-bisphosphate (see Fig. 14–7). behavior; they move randomly by Brownian motion. Diffusion The starting glyceraldehyde 3-phosphate must have been results in net movement of molecules from a region of higher labeled at C-1. The C-3 of dihydroxyacetone phosphate becomes concentration to a region of lower concentration simply because labeled through the triose phosphate isomerase reaction, thus it is more likely that a molecule on the high-concentration side giving rise to fructose 1,6-bisphosphate labeled at C-3. will enter the connecting channel. Look at this as a pathway 10. No. There would be no anaerobic production of ATP; aerobic with a rate-limiting step: the narrow end of the channel. The ATP production would be diminished only slightly. narrower end limits the rate at which molecules pass through 11. No. Lactate dehydrogenase is required to recycle NADϩ from because random motion of the molecules is less likely to move the NADH formed during the oxidation of glyceraldehyde them through the smaller cross section. The wide end of the 3-phosphate. channel does not act like a funnel for molecules, although it may 12. The transformation of glucose to lactate occurs when myocytes for fish, because molecules are not “crowded” by the sides of the are low in oxygen, and it provides a means of generating ATP narrowing funnel as fish would be. The narrow end limits the under O2-deficient conditions. Because lactate can be oxidized to rate of movement equally in both directions. When the pyruvate, glucose is not wasted; pyruvate is oxidized by aerobic concentrations on both sides are equal, the rates of movement reactions when O2 becomes plentiful. This metabolic flexibility in both directions are equal and there will be no change in gives the organism a greater capacity to adapt to its environment. concentration. (c) Fish exhibit nonrandom behavior, adjusting 13. It rapidly removes the 1,3-bisphosphoglycerate in a favorable their actions in response to the environment. Fish that enter the subsequent step, catalyzed by phosphoglycerate kinase. large opening of the channel tend to move forward because fish have behavior that tends to make them prefer forward 14. (a) 3-Phosphoglycerate is the product. (b) In the presence of movement, and they experience “crowding” as they move arsenate there is no net ATP synthesis under anaerobic conditions.

through the narrowing channel. It is easy for fish to enter the 15. (a) Ethanol fermentation requires 2 mol of Pi per mole of large opening, but they don’t move out of the trap as readily glucose. (b) Ethanol is the reduced product formed during ϩ because they are less likely to enter the small opening. reoxidation of NADH to NAD , and CO2 is the byproduct of (d) There are many possible explanations, some of which were the conversion of pyruvate to ethanol. Yes; pyruvate must be proposed by the letter-writers who criticized the article. Here converted to ethanol, to produce a continuous supply of are two: (1) The dye could bind to a molecule in the NADϩ for the oxidation of glyceraldehyde 3-phosphate. oligodendrocyte. Binding effectively removes the dye from the Fructose 1,6-bisphosphate accumulates; it is formed as an

bulk solvent, so it doesn’t “count” as a solute for thermodynamic intermediate in glycolysis. (c) Arsenate replaces Pi in the considerations yet remains visible in the fluorescence glyceraldehyde 3-phosphate dehydrogenase reaction to yield microscope. (2) The dye could be sequestered in a an acyl arsenate, which spontaneously hydrolyzes. This AbbreviatedSolutionsToProblems.indd Page AS-16 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-16 Abbreviated Solutions to Problems

prevents formation of ATP, but 3-phosphoglycerate continues glucose via pyruvate; this is a slower process, because formation through the pathway. of pyruvate is limited by NADϩ availability, the LDH equilibrium 16. Dietary niacin is used to synthesize NADϩ. Oxidations carried is in favor of lactate, and conversion of pyruvate to glucose is out by NADϩ are part of cyclic processes, with NADϩ as electron energy-requiring. (c) The equilibrium for the LDH reaction is in carrier (reducing agent); one molecule of NADϩ can oxidize favor of lactate formation. many thousands of molecules of glucose, and thus the dietary 27. Lactate is transformed to glucose in the liver by gluconeogenesis requirement for the precursor vitamin (niacin) is relatively small. (see Figs 14–16, 14–17). A defect in FBPase-1 would prevent 17. Dihydroxyacetone phosphate 1 NADH 1 Hϩ S glycerol entry of lactate into the gluconeogenic pathway in hepatocytes, 3-phosphate 1 NADϩ (catalyzed by a dehydrogenase) causing lactate to accumulate in the blood. 18. Galactokinase deficiency: galactose (less toxic); UDP-glucose: 28. Succinate is transformed to oxaloacetate, which passes into the galactose 1-phosphate uridylyl deficiency: galactose cytosol and is converted to PEP by PEP carboxykinase. Two 1-phosphate (more toxic). moles of PEP are then required to produce a mole of glucose by the route outlined in Fig. 14–17. 19. The proteins are degraded to amino acids and used for gluconeogenesis. 29. If the catabolic and anabolic pathways of glucose metabolism are 14 operating simultaneously, futile cycling of ATP occurs, with 20. (a) In the pyruvate carboxylase reaction, CO2 is added to extra O2 consumption. pyruvate, but PEP carboxykinase removes the same CO2 in the next step. Thus, 14C is not (initially) incorporated into glucose. 30. At the very least, accumulation of ribose 5-phosphate would tend to force this reaction in the reverse direction by mass Ϫ (b) COO action (see Eqn 13–4). It might also affect other metabolic CH CH CH reactions that involve ribose 5-phosphate as a substrate or 3 2 2 product—such as the pathways of nucleotide synthesis. 2Ϫ OC C O C OPO3 31. (a) Ethanol tolerance is likely to involve many more genes, and thus the engineering would be a much more involved 14 COOϪ 14 COOϪ 14 COOϪ project. (b) L-Arabinose isomerase (the araA enzyme) 14 1- C-Pyruvate Oxaloacetate Phosphoenolpyruvate converts an aldose to a ketose by moving the carbonyl of a nonphosphorylated sugar from C-1 to C-2. No analogous enzyme CH OPO2Ϫ is discussed in this chapter; all the enzymes described here act 2 3 on phosphorylated sugars. An enzyme that carries out a similar 2Ϫ H C OH CH2OPO3 CH2OH transformation with phosphorylated sugars is phosphohexose isomerase. L-Ribulokinase (araB) phosphorylates a sugar at C-5 14 2Ϫ CH OPO2Ϫ C OPO3 HCOH 3 by transferring the phosphate from ATP. Many such reactions O 14 COOϪ 14 COOϪ are described in this chapter, including the hexokinase reaction. L-Ribulose 5-phosphate epimerase (araD) switches the OH and 1,3-Bisphospho- 3-Phospho- 2-Phospho- O glycerate glycerate glycerate OH groups on a chiral carbon of a sugar. No analogous reaction is described in the chapter, but it is described in Chapter 20 (see Fig. 20–13). (c) The three ara enzymes would convert arabinose to xylulose 5-phosphate by the following L-arabinose isomerase L-ribulokinase pathway: Arabinose L-ribulose 2Ϫ epimerase CH2OPO3 L-ribulose 5-phosphate xylulose 5-phosphate. (d) The HCOH CH OPO2Ϫ arabinose is converted to xylulose 5-phosphate as in (c), which 2 3 enters the pathway in Fig. 14–23; the glucose 6-phosphate 14 C H C O product is then fermented to ethanol and CO2. (e) 6 molecules of arabinose 1 6 molecules of ATP are converted to 6 molecules 14 O 2OHCH of xylulose 5-phosphate, which feed into the pathway in Fig. Glyceraldehyde Dihydroxyacetone 14–23 to yield 5 molecules of glucose 6-phosphate, each of 3-phosphate phosphate which is fermented to yield 3 ATP (they enter as glucose 6-phosphate, not glucose)—15 ATP in all. Overall, you would expect a yield of 15 ATP 2 6 ATP 5 9 ATP from the 6 arabinose

2Ϫ 2Ϫ molecules. The other products are 10 molecules of ethanol and O3POH2C CH2OPO3 10 molecules of CO2. (f) Given the lower ATP yield, for an OHH C C O amount of growth (i.e., of available ATP) equivalent to growth 3,4-14C-Glucose without the added genes, the engineered Z. mobilis must HO 14 C 14 C OH ferment more arabinose, and thus it produces more ethanol. H H (g) One way to allow the use of xylose would be to add the genes for two enzymes: an analog of the araD enzyme that Fructose 1,6-bisphosphate converts xylose to ribose by switching the OH and OOH on C-3, and an analog of the araB enzyme that phosphorylates 21. 4 ATP equivalents per glucose molecule ribose at C-5. The resulting ribose 5-phosphate would feed into 22. Gluconeogenesis would be highly endergonic, and it would be the existing pathway. impossible to separately regulate gluconeogenesis and glycolysis. 23. The cell “spends” 1 ATP and 1 GTP in converting pyruvate to PEP. Chapter 15 24. (a), (b), (d) are glucogenic; (c) (e) are not. 1. (a) 0.0293 (b) 308 (c) No. Q is much lower than K9eq, indicating 25. Consumption of alcohol forces competition for NADϩ between that the PFK-1 reaction is far from equilibrium in cells; this ethanol metabolism and gluconeogenesis. The problem is reaction is slower than the subsequent reactions in glycolysis. compounded by strenuous exercise and lack of food, because at Flux through the glycolytic pathway is largely determined by the these times the level of blood glucose is already low. activity of PFK-1. Ϫ9 26. (a) The rapid increase in glycolysis; the rise in pyruvate and 2. (a) 1.4 3 10 M (b) The physiological concentration NADH results in a rise in lactate. (b) Lactate is transformed to (0.023 mM) is 16,000 times the equilibrium concentration; this AbbreviatedSolutionsToProblems.indd Page AS-17 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-17

reaction does not reach equilibrium in the cell. Many reactions decreasing [fructose 2,6-bisphosphate], which allosterically in the cell are not at equilibrium. stimulates phosphofructokinase and inhibits FBPase-1; this also accounts for the stimulation of gluconeogenesis. 3. In the absence of O2, the ATP needs are met by anaerobic glucose metabolism (fermentation to lactate). Because aerobic oxidation 13. (a) elevated (b) elevated (c) elevated of glucose produces far more ATP than does fermentation, less 14. (a) PKA cannot be activated in response to glucagon or glucose is needed to produce the same amount of ATP. epinephrine, and glycogen phosphorylase is not activated. 4. (a) There are two binding sites for ATP: a catalytic site and a (b) PP1 remains active, allowing it to dephosphorylate glycogen regulatory site. Binding of ATP to a regulatory site inhibits synthase (activating it) and glycogen phosphorylase (inhibiting it).

PFK-1, by reducing Vmax or increasing Km for ATP at the (c) Phosphorylase remains phosphorylated (active), increasing catalytic site. (b) Glycolytic flux is reduced when ATP is the breakdown of glycogen. (d) Gluconeogenesis cannot be plentiful. (c) The graph indicates that increased [ADP] stimulated when blood glucose is low, leading to dangerously suppresses the inhibition by ATP. Because the adenine low blood glucose during periods of fasting. nucleotide pool is fairly constant, consumption of ATP leads to 15. The drop in blood glucose triggers release of glucagon by the an increase in [ADP]. The data show that the activity of PFK-1 pancreas. In the liver, glucagon activates glycogen may be regulated by the [ATP]/[ADP] ratio. phosphorylase by stimulating its cAMP-dependent 5. The phosphate group of glucose 6-phosphate is completely phosphorylation and stimulates gluconeogenesis by lowering ionized at pH 7, giving the molecule an overall negative charge. [fructose 2,6-bisphosphate], thus stimulating FBPase-1. Because membranes are generally impermeable to electrically 16. (a) Reduced capacity to mobilize glycogen; lowered blood charged molecules, glucose 6-phosphate cannot pass from the glucose between meals (b) Reduced capacity to lower blood bloodstream into cells and hence cannot enter the glycolytic glucose after a carbohydrate meal; elevated blood glucose pathway and generate ATP. (This is why glucose, once (c) Reduced fructose 2,6-bisphosphate (F26BP) in liver, phosphorylated, cannot escape from the cell.) stimulating glycolysis and inhibiting gluconeogenesis 6. (a) In muscle: Glycogen breakdown supplies energy (ATP) via (d) Reduced F26BP, stimulating gluconeogenesis and glycolysis. Glycogen phosphorylase catalyzes the conversion of inhibiting glycolysis (e) Increased uptake of fatty acids and stored glycogen to glucose 1-phosphate, which is converted to glucose; increased oxidation of both (f) Increased conversion glucose 6-phosphate, an intermediate in glycolysis. During of pyruvate to acetyl-CoA; increased fatty acid synthesis. strenuous activity, skeletal muscle requires large quantities of 17. (a) Given that each particle contains about 55,000 glucose glucose 6-phosphate. In the liver: Glycogen breakdown maintains residues, the equivalent free glucose concentration would be a steady level of blood glucose between meals (glucose 55,000 3 0.01 M 5 550 mM, or 0.55 M. This would present a 6-phosphate is converted to free glucose). (b) In actively working serious osmotic challenge for the cell! (Body fluids have a muscle, ATP flux requirements are very high and glucose substantially lower osmolarity.) (b) The lower the number of 1-phosphate must be produced rapidly, requiring a high Vmax. branches, the lower the number of free ends available for

7. (a) [Pi]/[glucose 1-phosphate] 5 3.3/1 (b), (c) The value of this glycogen phosphorylase activity, and the slower the rate of ratio in the cell (.100:1) indicates that [glucose 1-phosphate] is glucose release. With no branches, there would be just one site far below the equilibrium value. The rate at which glucose for phosphorylase to act. (c) The outer tier of the particle 1-phosphate is removed (through entry into glycolysis) is would be too crowded with glucose residues for the enzyme to greater than its rate of production (by the glycogen gain access to cleave bonds and release glucose. (d) The phosphorylase reaction), so metabolite flow is from glycogen to number of chains doubles in each succeeding tier: tier 1 has one 0 1 2 glucose 1-phosphate. The glycogen phosphorylase reaction is chain (2 ), tier 2 has two (2 ), tier 3 has four (2 ), and so on. probably the regulatory step in glycogen breakdown. Thus, for t tiers, the number of chains in the outermost tier, CA, is 2tϪ1. (e) The total number of chains is 20 1 21 1 22 1 . . . 8. (a) increases (b) decreases (c) increases tϪ1 t 2 5 2 2 1. Each chain contains gc glucose molecules, so the 9. Resting: [ATP] high; [AMP] low; [acetyl-CoA] and [citrate] total number of glucose molecules, GT, is gc(2t – 1). (f) Glycogen intermediate. Running: [ATP] intermediate; [AMP] high; phosphorylase can release all but four of the glucose residues in [acetyl-CoA] and [citrate] low. Glucose flux through glycolysis a chain of length gc. Therefore, from each chain in the outer tier increases during the anaerobic sprint because (1) the ATP it can release (gc 2 4) glucose molecules. Given that there are inhibition of glycogen phosphorylase and PFK-1 is partially 2tϪ1 chains in the outer tier, the number of glucose molecules relieved, (2) AMP stimulates both enzymes, and (3) lower tϪ1 the enzyme can release, GPT, is (gc 2 4)(2 ). (g) The volume citrate and acetyl-CoA levels relieve their inhibitory effects on 4 3 of a sphere is ր3r . In this case, r is the thickness of one tier PFK-1 and pyruvate kinase, respectively. times the number of tiers, or (0.12gc 1 0.35)t nm. Thus 4 3 3 3 10. The migrating bird relies on the highly efficient aerobic Vs = ր3t (0.12gc 1 0.35) nm . (h) You can show algebraically oxidation of fats, rather than the anaerobic metabolism of that the value of gc that maximizes f is independent of t. glucose used by a sprinting rabbit. The bird reserves its muscle Choosing t 5 3: glycogen for short bursts of energy during emergencies.

11. Case A: (f), (3); Case B: (c), (3); Case C: (h), (4); Case D: gc CA GT GPT Vs f (d), (6) 5 4 35 4 11 5.8 12. (a) (1) Adipose: fatty acid synthesis slower. (2) Muscle: 6 4 42 8 19 9.7 glycolysis, fatty acid synthesis, and glycogen synthesis slower. 7 4 49 12 24 12 (3) Liver: glycolysis faster; gluconeogenesis, glycogen synthesis, 8 4 56 16 28 14 and fatty acid synthesis slower; pentose phosphate pathway 9 4 63 20 32 15 unchanged. (b) (1) Adipose and (3) liver: fatty acid synthesis 10 4 70 24 34 16 slower because lack of insulin results in inactive acetyl-CoA 11 4 77 28 36 16 carboxylase, the first enzyme of fatty acid synthesis. Glycogen 12 4 84 32 38 17 synthesis inhibited by cAMP-dependent phosphorylation (thus 13 4 91 36 40 17 activation) of glycogen synthase. (2) Muscle: glycolysis slower 14 4 98 40 41 17 because GLUT4 is inactive, so glucose uptake is inhibited. 15 4 100 44 42 16 (3) Liver: glycolysis slower because the bifunctional PFK-2/ 16 4 110 48 43 16 FBPase-2 is converted to the form with active FBPase-2, AbbreviatedSolutionsToProblems.indd Page AS-18 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-18 Abbreviated Solutions to Problems

The optimum value of gc (i.e., at maximum f) is 13. In nature, gc citric acid cycle. The addition of oxaloacetate or malate varies from 12 to 14, which corresponds to f values very close to stimulates the citric acid cycle and thus stimulates the optimum. If you choose another value for t, the numbers will respiration. The added oxaloacetate or malate serves a

differ but the optimal gc will still be 13. catalytic role, because it is regenerated in the latter part of the citric acid cycle. Chapter 16 Ϫ6 Ϫ8 10. (a) 5.6 3 10 (b) 1.1 3 10 M (c) 28 molecules 1. (a) ϩ 11. ADP (or GDP), P , CoA-SH, TPP, NAD ; not lipoic acid, which is 1 Citrate synthase: i covalently attached to the isolated enzymes that use it Acetyl-CoA 1 oxaloacetate 1 H2O S citrate 1 CoA 2 Aconitase: 12. The flavin nucleotides, FMN and FAD, would not be synthesized. Citrate S isocitrate Because FAD is required in the citric acid cycle, flavin 3 Isocitrate dehydrogenase: deficiency would strongly inhibit the cycle. ϩ Isocitrate 1 NAD S -ketoglutarate 1 CO2 1 NADH 13. Oxaloacetate might be withdrawn for aspartate synthesis or 4 -Ketoglutarate dehydrogenase: for gluconeogenesis. Oxaloacetate is replenished by the ϩ -Ketoglutarate 1 NAD 1 CoA S succinyl-CoA 1 CO2 1 NADH anaplerotic reactions catalyzed by PEP carboxykinase, PEP 5 Succinyl-CoA synthetase: carboxylase, malic enzyme, or pyruvate carboxylase (see

Succinyl-CoA 1 Pi 1 GDP S succinate 1 CoA 1 GTP Fig. 16–16). 6 Succinate dehydrogenase: 14. The terminal phosphoryl group in GTP can be transferred S Succinate 1 FAD fumarate 1 FADH2 to ADP in a reaction catalyzed by nucleoside diphosphate 7 Fumarase: kinase, with an equilibrium constant of 1.0: S Fumarate 1 H2O malate GTP 1 ADP S GDP 1 ATP 8 Malate dehydrogenase: 15. (a) ϪOOCOCH OCH OCOOϪ (succinate) (b) Malonate is a ϩ S ϩ 2 2 Malate 1 NAD oxaloacetate 1 NADH 1 H competitive inhibitor of succinate dehydrogenase. (c) A block (b), (c) 1 CoA, condensation; 2 none, isomerization; in the citric acid cycle stops NADH formation, which stops ϩ ϩ 3 NAD , oxidative decarboxylation; 4 NAD , CoA, and electron transfer, which stops respiration. (d) A large excess thiamine pyrophosphate, oxidative decarboxylation; 5 CoA, of succinate (substrate) overcomes the competitive inhibition. substrate-level phosphorylation; 6 FAD, oxidation; 7 none, 14 ϩ 16. (a) Add uniformly labeled [ C]glucose and check for the hydration; 8 NAD , oxidation 14 release of CO2. (b) Equally distributed in C-2 and C-3 of ϩ S (d) Acetyl-CoA 1 3NAD 1 FAD 1 GDP 1 Pi 1 2H2O oxaloacetate; an infinite number 2CO 1 CoA 1 3NADH 1 FADH 1 GTP 1 2Hϩ 2 2 17. Oxaloacetate equilibrates with succinate, in which C-1 and C-4 ϩ S 2. Glucose 1 4ADP 1 4Pi 1 10NAD 1 2FAD are equivalent. Oxaloacetate derived from succinate is labeled at 4ATP 1 10NADH 1 2FADH2 1 6CO2 C-1 and C-4, and the PEP derived from it has label at C-1, which 3. (a) Oxidation; methanol S formaldehyde 1 [HOH] gives rise to C-3 and C-4 of glucose. (b) Oxidation; formaldehyde S formate 1 [HOH] 18. (a) C-1 (b) C-3 (c) C-3 (d) C-2 (methyl group) (e) C-4 ϩ (c) Reduction; CO2 1 [HOH] S formate 1 H (f) C-4 (g) equally distributed in C-2 and C-3 ϩ (d) Reduction; glycerate 1 H 1 [HOH] S 19. Thiamine is required for the synthesis of TPP, a prosthetic glyceraldehyde 1 H2O group in the pyruvate dehydrogenase and -ketoglutarate (e) Oxidation; glycerol S dihydroxyacetone 1 [HOH] dehydrogenase complexes. A thiamine deficiency reduces the activity of these enzyme complexes and causes the observed (f) Oxidation; 2H O 1 toluene S benzoate 1 Hϩ 1 3[HOH] 2 accumulation of precursors. (g) Oxidation; succinate S fumarate 1 [HOH] 20. No. For every two carbons that enter as acetate, two leave the (h) Oxidation; pyruvate 1 H2O S acetate 1 CO2 1 [HOH] cycle as CO2; thus there is no net synthesis of oxaloacetate. Net 4. From the structural formulas, we see that the carbon-bound H/C synthesis of oxaloacetate occurs by the carboxylation of ratio of hexanoic acid (11/6) is higher than that of glucose (7/6). pyruvate, an anaplerotic reaction. Hexanoic acid is more reduced and yields more energy on 21. Yes, the citric acid cycle would be inhibited. Oxaloacetate is complete combustion to CO and H O. 2 2 present at relatively low concentrations in mitochondria, and ϩ S ϩ 5. (a) Oxidized; ethanol 1 NAD acetaldehyde 1 NADH 1 H removing it for gluconeogenesis would tend to shift the ϩ (b) Reduced; 1,3-bisphosphoglycerate 1 NADH 1 H S equilibrium for the citrate synthase reaction toward ϩ 2Ϫ glyceraldehyde 3-phosphate 1 NAD 1 HPO4 oxaloacetate. ϩ S (c) Unchanged; pyruvate 1 H acetaldehyde 1 CO2 22. (a) Inhibition of aconitase (b) Fluorocitrate; competes with (d) Oxidized; pyruvate 1 NADϩ S citrate; by a large excess of citrate (c) Citrate and fluorocitrate ϩ acetate 1 CO2 1 NADH 1 H are inhibitors of PFK-1. (d) All catabolic processes necessary (e) Reduced; oxaloacetate 1 NADH 1 Hϩ S malate 1 NADϩ for ATP production are shut down. ϩ 23. Glycolysis: (f) Unchanged; acetoacetate 1 H S acetone 1 CO2 ϩ S 6. TPP: thiazolium ring adds to carbon of pyruvate, then Glucose 1 2Pi 1 2ADP 1 2NAD ϩ stabilizes the resulting carbanion by acting as an electron sink. 2 pyruvate 1 2ATP 1 2NADH 1 2H 1 2H2O Lipoic acid: oxidizes pyruvate to level of acetate (acetyl- Pyruvate carboxylase reaction: S CoA), and activates acetate as a thioester. CoA-SH: activates 2 Pyruvate 1 2CO2 1 2ATP 1 2H2O ϩ acetate as thioester. FAD: oxidizes lipoic acid. NAD : oxidizes 2 oxaloacetate 1 2ADP 1 2Pi 1 4H FAD. Malate dehydrogenase reaction: ϩ ϩ 7. Lack of TPP inhibits pyruvate dehydrogenase; pyruvate 2 Oxaloacetate 1 2NADH 1 2H S 2 L-malate 1 2NAD accumulates. This recycles nicotinamide coenzymes under anaerobic 8. Oxidative decarboxylation; NADϩ or NADPϩ; -ketoglutarate conditions. The overall reaction is ϩ dehydrogenase Glucose 1 2CO2 S 2 L-malate 1 4H 9. Oxygen consumption is a measure of the activity of the This produces four Hϩ per glucose, increasing the acidity and first two stages of cellular respiration: glycolysis and the thus the tartness of the wine. AbbreviatedSolutionsToProblems.indd Page AS-19 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-19

ϩ 24. Net reaction: 2 Pyruvate 1 ATP 1 2NAD 1 H2O S for cellular respiration in this system. (d) Experiment I: ϩ -ketoglutarate 1 CO2 1 ADP 1 Pi 1 2NADH 1 3H Citrate is causing much more O2 consumption than would be 25. The cycle participates in catabolic and anabolic processes. For expected from its complete oxidation. Each molecule of example, it generates ATP by substrate oxidation, but also Citrate seems to be acting as though it were more than one provides precursors for amino acid synthesis (see Fig. 16–16). molecule. The only possible explanation is that each molecule of citrate functions more than once in the reaction—which is 26. (a) decreases (b) increases (c) decreases how a catalyst operates. Experiment II: The key is to 27. (a) Citrate is produced through the action of citrate synthase on calculate the excess O2 consumed by each sample compared oxaloacetate and acetyl-CoA. Citrate synthase can be used for with the control (sample 1). net synthesis of citrate when (1) there is a continuous influx of new oxaloacetate and acetyl-CoA and (2) isocitrate synthesis is Substrate(s) ␮L O2 Excess ␮L restricted, as in a medium low in Fe3ϩ. Aconitase requires Fe3ϩ, Sample added absorbed O2 consumed so an Fe3ϩ-restricted medium restricts the synthesis of aconitase. 1 No extra 342 0 (b) Sucrose 1 H2O S glucose 1 fructose ϩ 2 0.3 mL 0.2 M Glucose 1 2Pi 1 2ADP 1 2NAD S ϩ 1-phosphoglycerol 757 415 2 pyruvate 1 2ATP 1 2NADH 1 2H 1 2H2O ϩ 3 0.15 mL 0.02 M citrate 431 89 Fructose 1 2Pi 1 2ADP 1 2NAD S ϩ 4 0.3 mL 0.2 M 2 pyruvate 1 2ATP 1 2NADH 1 2H 1 2H2O ϩ 1-phosphoglycerol 2 Pyruvate 1 2NAD 1 2CoA S ϩ 1 0.15 mL 0.02 M citrate 1,385 1,043 2 acetyl-CoA 1 2NADH 1 2H 1 2CO2 2 Pyruvate 1 2CO2 1 2ATP 1 2H2O S ϩ 2 oxaloacetate 1 2ADP 1 2Pi 1 4H If both citrate and 1-phosphoglycerol were simply substrates for 2 Acetyl-CoA 1 2 oxaloacetate 1 2H2O S 2 citrate 1 2CoA the reaction, you would expect the excess O2 consumption by The overall reaction is sample 4 to be the sum of the individual excess consumptions by ϩ samples 2 and 3 (415 L 1 89 L 5 504 L). However, the Sucrose 1 H2O 1 2Pi 1 2ADP 1 6NAD S ϩ excess consumption when both substrates are present is roughly 2 citrate 1 2ATP 1 6NADH 1 10H ϩ twice this amount (1,043 L). Thus citrate increases the ability of (c) The overall reaction consumes NAD . Because the cellular the tissue to metabolize 1-phosphoglycerol. This behavior is pool of this oxidized coenzyme is limited, it must be recycled by typical of a catalyst. Both experiments (I and II) are required to the electron-transfer chain with consumption of O2. make this case convincing. Based on experiment I only, citrate is Consequently, the overall conversion of sucrose to citric acid is somehow accelerating the reaction, but it is not clear whether it an aerobic process and requires molecular oxygen. acts by helping substrate metabolism or by some other 28. Succinyl-CoA is an intermediate of the citric acid cycle; its mechanism. Based on experiment II only, it is not clear which accumulation signals reduced flux through the cycle, calling for molecule is the catalyst, citrate or 1-phosphoglycerol. Together, reduced entry of acetyl-CoA into the cycle. Citrate synthase, by the experiments show that citrate is acting as a “catalyst” for the regulating the primary oxidative pathway of the cell, regulates the oxidation of 1-phosphoglycerol. (e) Given that the pathway can supply of NADH and thus the flow of electrons from NADH to O2. consume citrate (see sample 3), if citrate is to act as a catalyst it 29. Fatty acid catabolism increases [acetyl-CoA], which stimulates must be regenerated. If the set of reactions first consumes then pyruvate carboxylase. The resulting increase in [oxaloacetate] regenerates citrate, it must be a circular rather than a linear stimulates acetyl-CoA consumption by the citric acid cycle, pathway. (f) When the pathway is blocked at -ketoglutarate and [citrate] rises, inhibiting glycolysis at the level of PFK-1. dehydrogenase, citrate is converted to -ketoglutarate but the In addition, increased [acetyl-CoA] inhibits the pyruvate pathway goes no further. Oxygen is consumed by reoxidation of dehydrogenase complex, slowing the utilization of pyruvate the NADH produced by isocitrate dehydrogenase. from glycolysis. (g) Citrate 30. Oxygen is needed to recycle NADϩ from the NADH produced -Ketoglutarate by the oxidative reactions of the citric acid cycle. Reoxidation Glucose ? ? ? of NADH occurs during mitochondrial oxidative phosphorylation. Succinate 31. Increased [NADH]/[NADϩ] inhibits the citric acid cycle by mass action at the three NADϩ-reducing steps; high [NADH] shifts ϩ Oxaloacetate equilibrium toward NAD . Fumarate 32. Toward citrate; DG for the citrate synthase reaction under these conditions is about 28 kJ/mol. Malonate 33. Steps 4 and 5 are essential in the reoxidation of the enzyme’s This differs from Fig. 16–7 in that it does not include cis- reduced lipoamide cofactor. aconitate and isocitrate (between citrate and -ketoglutarate), 34. The citric acid cycle is so central to metabolism that a serious or succinyl-CoA, or acetyl-CoA. (h) Establishing a quantitative defect in any cycle enzyme would probably be lethal to the conversion was essential to rule out a branched or other, more embryo. complex pathway. 35. The first enzyme in each path is under reciprocal allosteric regulation. Inhibition of one path shunts isocitrate into the other Chapter 17 path. 1. The fatty acid portion; the carbons in fatty acids are more reduced than those in glycerol. 36. (a) The only reaction in muscle tissue that consumes 2. (a) 4.0 3 105 kJ (9.6 3 104 kcal) (b) 48 days (c) 0.48 lb/day significant amounts of oxygen is cellular respiration, so O2 consumption is a good proxy for respiration. (b) Freshly 3. The first step in fatty acid oxidation is analogous to the

prepared muscle tissue contains some residual glucose; O2 conversion of succinate to fumarate; the second step, to the consumption is due to oxidation of this glucose. (c) Yes. conversion of fumarate to malate; the third step, to the

Because the amount of O2 consumed increased when citrate conversion of malate to oxaloacetate. or 1-phosphoglycerol was added, both can serve as substrate 4. 8 cycles; the last releases 2 acetyl-CoA. AbbreviatedSolutionsToProblems.indd Page AS-20 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-20 Abbreviated Solutions to Problems

Ϫ 5. (a) ROCOO 1 ATP S acyl-AMP 1 PPi 20. Ser to Ala: blocks oxidation in mitochondria. Ser to Asp: Acyl-AMP 1 CoA S acyl-CoA 1 AMP blocks fatty acid synthesis, stimulates oxidation.

(b) Irreversible hydrolysis of PPi to 2Pi by cellular inorganic 21. Response to glucagon or epinephrine would be prolonged, giving pyrophosphatase a greater mobilization of fatty acids in adipocytes. 6. cis-D3-Dodecanoyl-CoA; it is converted to cis-D2-dodecanoyl- 22. Enz-FAD, having a more positive standard reduction ϩ CoA, then -hydroxydodecanoyl-CoA. potential, is a better electron acceptor than NAD , and the 7. 4 acetyl-CoA and 1 propionyl-CoA reaction is driven in the direction of fatty acyl–CoA oxidation. This more favorable equilibrium is obtained at the cost of 1 8. Yes. Some of the tritium is removed from palmitate during the ATP; only 1.5 ATP are produced per FADH oxidized in the dehydrogenation reactions of oxidation. The removed tritium 2 respiratory chain (vs. 2.5 per NADH). appears as tritiated water. 23. 9 turns; arachidic acid, a 20-carbon saturated fatty acid, yields 10 9. Fatty acyl groups condensed with CoA in the cytosol are first molecules of acetyl-CoA, the last two formed in the ninth turn. transferred to carnitine, releasing CoA, then transported into the mitochondrion, where they are again condensed with CoA. 24. See Fig. 17–12. [3-14C]Succinyl-CoA is formed, which gives rise The cytosolic and mitochondrial pools of CoA are thus kept to oxaloacetate labeled at C-2 and C-3. separate, and no radioactive CoA from the cytosolic pool enters 25. Phytanic acid S pristanic acid S propionyl-CoA S S S succinyl- the mitochondrion. CoA S succinate S fumarate S malate. All malate carbons 10. (a) In the pigeon, oxidation predominates; in the pheasant, would be labeled, but C-1 and C-4 would have only half as much anaerobic glycolysis of glycogen predominates. (b) Pigeon muscle label as C-2 and C-3. would consume more O2. (c) Fat contains more energy per gram 26. ATP hydrolysis in the energy-requiring reactions of a cell takes than glycogen does. In addition, the anaerobic breakdown of up water in the reaction ATP 1 H2O S ADP 1 Pi; thus, in the glycogen is limited by the tissue’s tolerance to lactate buildup. steady state, there is no net production of H2O. Thus the pigeon, operating on the oxidative catabolism of fats, is 27. Methylmalonyl-CoA mutase requires the cobalt-containing the long-distance flyer. (d) These enzymes are the regulatory cofactor formed from vitamin B . enzymes of their respective pathways and thus limit ATP 12 production rates. 28. Mass lost per day is about 0.66 kg, or about 140 kg in 11. Malonyl-CoA would no longer inhibit fatty acid entry into the 7 months. Ketosis could be avoided by degradation of mitochondrion and oxidation, so there might be a futile cycle nonessential body proteins to supply amino acid skeletons for of simultaneous fatty acid synthesis in the cytosol and fatty acid gluconeogenesis. breakdown in mitochondria. 29. (a) Fatty acids are converted to their CoA derivatives by 12. (a) The carnitine-mediated entry of fatty acids into enzymes in the cytoplasm; the acyl-CoAs are then imported mitochondria is the rate-limiting step in fatty acid oxidation. into mitochondria for oxidation. Given that the researchers Carnitine deficiency slows fatty acid oxidation; added carnitine were using isolated mitochondria, they had to use CoA increases the rate. (b) All increase the metabolic need for fatty derivatives. (b) Stearoyl-CoA was rapidly converted to 9 acetyl- acid oxidation. (c) Carnitine deficiency might result from a CoA by the -oxidation pathway. All intermediates reacted deficiency of lysine, its precursor, or from a defect in one of the rapidly and none were detectable at significant levels. (c) Two enzymes in the biosynthesis of carnitine. rounds. Each round removes two carbon atoms, thus two rounds convert an 18-carbon to a 14-carbon fatty acid and 2 13. Oxidation of fats releases metabolic water; 1.4 L of water per kg acetyl-CoA. (d) The K is higher for the trans isomer than for of tripalmitoylglycerol (ignores the small contribution of glycerol m the cis, so a higher concentration of trans isomer is required for to the mass). the same rate of breakdown. Roughly speaking, the trans 14. The bacteria can be used to completely oxidize hydrocarbons to isomer binds less well than the cis, probably because CO2 and H2O. However, contact between hydrocarbons and differences in shape, even though not at the target site for the bacterial enzymes may be difficult to achieve. Bacterial nutrients enzyme, affect substrate binding to the enzyme. (e) The such as nitrogen and phosphorus may be limiting and inhibit substrate for LCAD/VLCAD builds up differently, depending on growth. the particular substrate; this is expected for the rate-limiting 15. (a) Mr 136; phenylacetic acid (b) Even step in a pathway. (f) The kinetic parameters show that the 16. Because the mitochondrial pool of CoA is small, CoA must be trans isomer is a poorer substrate than the cis for LCAD, but recycled from acetyl-CoA via the formation of ketone bodies. there is little difference for VLCAD. Because it is a poorer This allows the operation of the -oxidation pathway, necessary substrate, the trans isomer accumulates to higher levels than for energy production. the cis. (g) One possible pathway is shown below (indicating 17. (a) Glucose yields pyruvate via glycolysis, and pyruvate is the “inside” and “outside” mitochondria). main source of oxaloacetate. Without glucose in the diet, [oxaloacetate] drops and the citric acid cycle slows. (b) Odd- Elaidoyl-CoA carnitine acyltransferase I elaidoyl-carnitine transport numbered; propionate conversion to succinyl-CoA provides (outside) (outside) intermediates for the citric acid cycle and four-carbon carnitine acyltransferase II 2 rounds of oxidation precursors for gluconeogenesis. elaidoyl-carnitine elaidoyl-CoA (inside) (inside) 18. For the odd-chain heptanoic acid, oxidation produces propionyl-CoA, which can be converted in several steps to 5-trans-tetradecenoyl-CoA thioesterase 5-trans-tetradecanoic acid diffusion oxaloacetate, a starting material for gluconeogenesis. The even- (inside) (inside) chain fatty acid cannot support gluconeogenesis, because it is entirely oxidized to acetyl-CoA. 5-trans-tetradecanoic acid 19. Oxidation of -fluorooleate forms fluoroacetyl-CoA, which (outside) enters the citric acid cycle and produces fluorocitrate, a powerful inhibitor of aconitase. Inhibition of aconitase shuts down the (h) It is correct insofar as trans fats are broken down less efficiently citric acid cycle. Without reducing equivalents from the citric than cis fats, and thus trans fats may “leak” out of mitochondria. It acid cycle, oxidative phosphorylation (ATP synthesis) is fatally is incorrect to say that trans fats are not broken down by cells; they slowed. are broken down, but at a slower rate than cis fats. AbbreviatedSolutionsToProblems.indd Page AS-21 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-21

Chapter 18 aminotransferase. Approximately one-half of all the amino groups 1. excreted as urea must pass through the aspartate aminotransferase O reaction, making this the most highly active aminotransferase. Ϫ Ϫ (a) OOC CH2 C COO Oxaloacetate 9. (a) A person on a diet consisting only of protein must use amino acids as the principal source of metabolic fuel. Because the O catabolism of amino acids requires the removal of nitrogen as urea, the process consumes abnormally large quantities of water to dilute Ϫ Ϫ (b) OOC CH2 CH2 C COO -Ketoglutarate and excrete the urea in the urine. Furthermore, electrolytes in the “liquid protein” must be diluted with water and excreted. If the daily O water loss through the kidney is not balanced by a sufficient water B intake, a net loss of body water results. (b) When considering the (c) Ϫ CH3 C COO Pyruvate nutritional benefits of protein, one must keep in mind the total amount of amino acids needed for protein synthesis and the O distribution of amino acids in the dietary protein. Gelatin contains a nutritionally unbalanced distribution of amino acids. As large (d ) Ϫ p CH2 C COO Phenyl yruvate amounts of gelatin are ingested and the excess amino acids are catabolized, the capacity of the urea cycle may be exceeded, leading 2. This is a coupled-reaction assay. The product of the slow to ammonia toxicity. This is further complicated by the dehydration transamination (pyruvate) is rapidly consumed in the that may result from excretion of large quantities of urea. A subsequent “indicator reaction” catalyzed by lactate combination of these two factors could produce coma and death. dehydrogenase, which consumes NADH. Thus the rate of 10. Lysine and leucine disappearance of NADH is a measure of the rate of the 11. (a) Phenylalanine hydroxylase; a low-phenylalanine diet aminotransferase reaction. The indicator reaction is monitored (b) The normal route of phenylalanine metabolism via by observing the decrease in absorption of NADH at 340 nm hydroxylation to tyrosine is blocked, and phenyalanine with a spectrophotometer. accumulates. (c) Phenylalanine is transformed to 3. Alanine and glutamine play special roles in the transport of phenylpyruvate by transamination, and then to phenyllactate by amino groups from muscle and from other nonhepatic tissues, reduction. The transamination reaction has an equilibrium respectively, to the liver. constant of 1.0, and phenylpyruvate is formed in significant 4. No. The nitrogen in alanine can be transferred to oxaloacetate amounts when phenylalanine accumulates. (d) Because of the via transamination, to form aspartate. deficiency in production of tyrosine, which is a precursor of 5. 15 mol of ATP per mole of lactate; 13 mol of ATP per mole of melanin, the pigment normally present in hair. alanine, when nitrogen removal is included 12. Catabolism of the carbon skeletons of valine, methionine, and 6. (a) Fasting resulted in low blood glucose; subsequent isoleucine is impaired because a functional methylmalonyl-CoA administration of the experimental diet led to rapid catabolism mutase (a coenzyme B12 enzyme) is absent. The physiological of glucogenic amino acids. (b) Oxidative deamination caused effects of loss of this enzyme are described in Table 18–2 and Box 18–2. the rise in NH3 levels; the absence of arginine (an intermediate in the urea cycle) prevented conversion of NH3 to urea; 13. The vegan diet lacks vitamin B12, leading to the increase in arginine is not synthesized in sufficient quantities in the cat to homocysteine and methylmalonate (reflecting the deficiencies in meet the needs imposed by the stress of the experiment. This methionine synthase and methylmalonic acid mutase, suggests that arginine is an essential amino acid in the cat’s respectively) in individuals on the diet for several years. Dairy

diet. (c) Ornithine is converted to arginine by the urea cycle. products provide some vitamin B12 in the lactovegetarian diet. ϩ 7. H2O 1 glutamate 1 NAD S 14. The genetic forms of pernicious anemia generally arise as a result ϩ ϩ -ketoglutarate 1 NH 4 1 NADH 1 H of defects in the pathway that mediates absorption of dietary ϩ NH4 1 2ATP 1 H2O 1 CO2 S vitamin B12 (see Box 17–2). Because dietary supplements are not ϩ carbamoyl phosphate 1 2ADP 1 Pi 1 3H absorbed in the intestine, these conditions are treated by ϩ Carbamoyl phosphate 1 ornithine S citrulline 1 Pi 1 H injecting supplementary B12 directly into the bloodstream. Citrulline 1 aspartate 1 ATP S 15. The mechanism is identical to that for serine dehydratase (see ϩ argininosuccinate 1 AMP 1 PPi 1 H Fig. 18–20a) except that the extra methyl group of threonine is Argininosuccinate S arginine 1 fumarate retained, yielding -ketobutyrate instead of pyruvate. S Fumarate 1 H2O malate 15 15 ϩ ϩ 16. (a) NH CO NH Malate 1 NAD S oxaloacetate 1 NADH 1 H 2 2 Oxaloacetate 1 glutamate S aspartate 1 -ketoglutarate (b) Ϫ 14 14 Ϫ Arginine 1 H2O S urea 1 ornithine OO C CH2 CH2 COO ϩ S 2 Glutamate 1 CO2 1 4H2O 1 2NAD 1 3ATP 15 ϩ NH 2 -ketoglutarate 1 2NADH 1 7H 1 urea 1 2ADP 1 15 AMP 1 PPi 1 2Pi (1) (c) R NH C NH2 Additional reactions that need to be considered: AMP 1 ATP S 2ADP (2) O ϩ O2 1 8H 1 2NADH 1 6ADP 1 6Pi S ϩ (d) RCNH 15NH 2NAD 1 6ATP 1 8H2O (3) 2 ϩ H2O 1 PPi S 2Pi 1 H (4) Summing equations (1) through (4), (e) No label

2 Glutamate 1 CO2 1 O2 1 2ADP 1 2Pi S 15 2 -ketoglutarate 1 urea 1 3H2O 1 2ATP NH2 8. The second amino group introduced into urea is transferred from Ϫ 14 14 Ϫ (f) OO C C CH2 COO aspartate, which is generated during the transamination of glutamate to oxaloacetate, a reaction catalyzed by aspartate H AbbreviatedSolutionsToProblems.indd Page AS-22 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-22 Abbreviated Solutions to Problems

1 2 3 4 5 6 to reverse of citrate synthase reaction in the citric acid cycle; 17. (a) Isoleucine ¡ II ¡ IV ¡ I ¡ V ¡ III ¡ no cofactors acetyl-CoA 1 propionyl-CoA (b) Step 1 transamination, no 20. (a) Leucine; valine; isoleucine (b) Cysteine (derived from analogous reaction, PLP; 2 oxidative decarboxylation, analogous cystine). If cysteine were decarboxylated as shown in Fig. 18–6, ϩ to the pyruvate dehydrogenase reaction, NAD , TPP, lipoate, it would yield H3NOCH2OCH2OSH, which could be oxidized to FAD; 3 oxidation, analogous to the succinate dehydrogenase taurine. (c) The January 1957 blood shows significantly reaction, FAD; 4 hydration, analogous to the fumarase reaction, elevated levels of isoleucine, leucine, methionine, and valine; the no cofactor; 5 oxidation, analogous to the malate dehydrogenase January 1957 urine, significantly elevated isoleucine, leucine, reaction, NADϩ; 6 thiolysis (reverse aldol condensation), taurine, and valine. (d) All patients had high levels of analogous to the thiolase reaction, CoA. isoleucine, leucine, and valine in both blood and urine, suggesting a defect in the breakdown of these amino acids. 18. A likely mechanism is: Enz Given that the urine also contained high levels of the keto forms of these three amino acids, the block in the pathway H Lys N must occur after deamination but before dehydrogenation ϩ H OH ϩ (as shown in Fig. 18–28). (e) The model does not explain the Lys CH NH3 high levels of methionine in blood and taurine in urine. The ϪOOC C C H ϩ HO high taurine levels may be due to the death of brain cells during ϩ P NH3 H Enz the end stage of the disease. However, the reason for high ϩ levels of methionine in blood are unclear; the pathway of Serine CH N 3 H methionine degradation is not linked with the degradation of PLP branched-chain amino acids. Increased methionine could be a secondary effect of buildup of the other amino acids. It is important to keep in mind that the January 1957 samples were from an individual who was dying, so comparing blood and urine results with those of a healthy individual may not be H appropriate. (f) The following information is needed (and was B Enz eventually obtained by other workers): (1) The dehydrogenase H O H activity is significantly reduced or missing in individuals with ϪOOC C HC ϪOOC CϪ maple syrup urine disease. (2) The disease is inherited as a single-gene defect. (3) The defect occurs in a gene encoding all ϩ O ϩ ϩ NH H NH HB Enz or part of the dehydrogenase. (4) The genetic defect leads to C H CH CH production of inactive enzyme. H HO C HO C Chapter 19 P P 1. Reaction (1): (a), (d) NADH; (b), (e) E-FMN; (c) NADϩ/NADH

ϩ ϩ and E-FMN/FMNH2 ϩ CH3 N CH3 N 3 H H Reaction (2): (a), (d) E-FMNH2; (b), (e) Fe ; (c) E-FMN/ 3ϩ 2ϩ FMNH2 and Fe /Fe 2ϩ 3ϩ 2ϩ Reaction (3): (a), (d) Fe ; (b), (e) Q; (c) Fe /Fe and Q/QH2 2. The side chain makes ubiquinone soluble in lipids and allows it to diffuse in the semifluid membrane. H Glycine 3. From the difference in standard reduction potential (DE98) for Enz ϪOOC C H H each pair of half-reactions, one can calculate DG98. The oxidation of succinate by FAD is favored by the negative ϩ Lys Ϫ H NH OOC C H N standard free-energy change (DG98 5 23.7 kJ/mol). Oxidation ϩ ϩ ϩ ϩ by NAD would require a large, positive, standard free-energy CH NH NH Lys CH 3 3 change (DG98 5 68 kJ/mol). HO HO 4. (a) All carriers reduced; CNϪ blocks the reduction of O P P 2 Enz catalyzed by cytochrome oxidase. (b) All carriers reduced; in ϩ ϩ the absence of O2, the reduced carriers are not reoxidized. CH3 N CH3 N H H (c) All carriers oxidized. (d) Early carriers more reduced; later PLP carriers more oxidized. 5. (a) Inhibition of NADH dehydrogenase by rotenone decreases The formaldehyde (HCHO) produced in the second step reacts the rate of electron flow through the respiratory chain, which in rapidly with tetrahydrofolate at the enzyme active site to turn decreases the rate of ATP production. If this reduced rate produce N5, N10-methylenetetrahydrofolate (see Fig. 18–17). is unable to meet the organism’s ATP requirements, the 19. (a) Transamination; no analogies; PLP. (b) Oxidative organism dies. (b) Antimycin A strongly inhibits the oxidation decarboxylation; analogous to oxidative decarboxylation of of Q in the respiratory chain, reducing the rate of electron pyruvate to acetyl-CoA prior to entry into the citric acid cycle, transfer and leading to the consequences described in (a). and of -ketoglutarate to succinyl-CoA in the citric acid cycle; (c) Because antimycin A blocks all electron flow to oxygen, it is NADϩ, FAD, lipoate, and TPP. (c) Dehydrogenation a more potent poison than rotenone, which blocks electron flow (oxidation); analogous to dehydrogenation of succinate to from NADH but not from FADH2. fumarate in the citric acid cycle, and of fatty acyl–CoA to 6. (a) The rate of electron transfer necessary to meet the ATP enoyl-CoA in oxidation; FAD. (d) Carboxylation; no demand increases, and thus the P/O ratio decreases. (b) High analogies in citric acid cycle or oxidation; ATP and biotin. concentrations of uncoupler produce P/O ratios near zero. The (e) Hydration; analogous to hydration of fumarate to malate in P/O ratio decreases, and more fuel must be oxidized to generate the citric acid cycle, and of enoyl-CoA to 3-hydroxyacyl-CoA in the same amount of ATP. The extra heat released by this oxidation; no cofactors. (f) Reverse aldol reaction; analogous oxidation raises the body temperature. (c) Increased activity of AbbreviatedSolutionsToProblems.indd Page AS-23 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

Abbreviated Solutions to Problems AS-23

the respiratory chain in the presence of an uncoupler requires 25. Defects in Complex II result in increased production of ROS, the degradation of additional fuel. By oxidizing more fuel damage to DNA, and mutations that lead to unregulated cell (including fat reserves) to produce the same amount of ATP, division (cancer; see Section 12.12). It is not clear why the the body loses weight. When the P/O ratio approaches zero, the cancer tends to occur in the midgut. lack of ATP results in death. 26. For the maximum photosynthetic rate, PSI (which absorbs light 7. Valinomycin acts as an uncoupler. It combines with Kϩ to form a of 700 nm) and PSII (which absorbs light of 680 nm) must be complex that passes through the inner mitochondrial membrane, operating simultaneously. dissipating the membrane potential. ATP synthesis decreases, 27. The extra weight comes from the water consumed in the overall which causes the rate of electron transfer to increase. This reaction. results in an increase in the Hϩ gradient, O consumption, and 2 28. Purple sulfur bacteria use H S as the hydrogen donor in amount of heat released. 2 photosynthesis. No O2 is evolved, because the single 8. (a) The formation of ATP is inhibited. (b) The formation of photosystem lacks the manganese-containing water-splitting ATP is tightly coupled to electron transfer: 2,4-dinitrophenol is complex. an uncoupler of oxidative phosphorylation. (c) Oligomycin 29. 0.44 9. Cytosolic malate dehydrogenase plays a key role in the transport 30. (a) Stops (b) Slows; some electron flow continues by the cyclic of reducing equivalents across the inner mitochondrial pathway. membrane via the malate-aspartate shuttle. 31. During illumination, a proton gradient is established. When ADP 10. (a) Glycolysis becomes anaerobic. (b) Oxygen consumption and P are added, ATP synthesis is driven by the gradient, which ceases. (c) Lactate formation increases. (d) ATP synthesis i becomes exhausted in the absence of light. decreases to 2 ATP/glucose. 32. DCMU blocks electron transfer between PSII and the first site of 11. The steady-state concentration of P in the cell is much higher i ATP production. than that of ADP. The Pi released by ATP hydrolysis changes 33. In the presence of venturicidin, proton movement through the total [Pi] very little. CF CF complex is blocked, and electron flow (oxygen 12. The response to (a) increased [ADP] is faster because the o 1 evolution) continues only until the free-energy cost of pumping response to (b) reduced pO requires protein synthesis. 2 protons against the rising proton gradient equals the free energy 13. (a) NADH is reoxidized via electron transfer instead of lactic available in a photon. DNP, by dissipating the proton gradient, acid fermentation. (b) Oxidative phosphorylation is more restores electron flow and oxygen evolution. efficient. (c) The high mass-action ratio of the ATP system 34. (a) 56 kJ/mol (b) 0.29 V inhibits phosphofructokinase-1. 35. From the difference in reduction potentials, one can calculate 14. Fermentation to ethanol could be accomplished in the presence that DG98 5 15 kJ/mol for the redox reaction. Fig. 19–48 shows of O , which is an advantage because strict anaerobic conditions 2 that the energy of photons in any region of the visible spectrum is are difficult to maintain. The Pasteur effect is not observed, more than sufficient to drive this endergonic reaction. since the citric acid cycle and electron-transfer chain are Ϫ77 inactive. 36. 1.35 3 10 ; the reaction is highly unfavorable! In chloroplasts, the input of light energy overcomes this barrier. 15. More-efficient electron transfer between complexes. Ϫ8 Ϫ8 37. 2920 kJ/mol 16. (a) External medium: 4.0 3 10 M; matrix: 2.0 3 10 M ϩ (b) [H ] gradient contributes 1.7 kJ/mol toward ATP synthesis 38. No. The electrons from H2O flow to the artificial electron 3ϩ ϩ (c) 21 (d) No (e) From the overall transmembrane potential acceptor Fe , not to NADP . 8 17. (a) 0.91 mol/s и g (b) 5.5 s; to provide a constant level of ATP, 39. About once every 0.1 s; 1 in 10 is excited. regulation of ATP production must be tight and rapid. 40. Light of 700 nm excites PSI but not PSII; electrons flow from ϩ 18. 53 mol/s и g. With a steady state [ATP] of 7.0 mol/g, this is P700 to NADP , but no electrons flow from P680 to replace equivalent to 10 turnovers of the ATP pool per second; the them. When light of 680 nm excites PSII, electrons tend to flow reservoir would last about 0.13 s. to PSI, but the electron carriers between the two photosystems quickly become completely reduced. 19. Reactive oxygen species react with macromolecules, including DNA. If a mitochondrial defect leads to increased production of 41. No. The excited electron from P700 returns to refill the electron ROS, the nuclear genes that encode proto-oncogenes can be “hole” created by illumination. PSII is not needed to supply damaged, producing oncogenes and leading to unregulated cell electrons, and no O2 is evolved from H2O. NADPH is not formed, division and cancer (see Section 12.12). because the excited electron returns to P700. 2ϩ 20. Different extents of heteroplasmy for the defective gene 42. (a) (1) The presence of Mg supports the hypothesis that produce different degrees of defective mitochondrial function. chlorophyll is directly involved in catalysis of the phosphorylation reaction: ADP 1 Pi S ATP. (2) Many enzymes 21. The inner mitochondrial membrane is impermeable to NADH, 2ϩ but the reducing equivalents of NADH are transferred (shuttled) (or other proteins) that contain Mg are not phosphorylating enzymes, so the presence of Mg2ϩ in chlorophyll does not prove through the membrane indirectly: they are transferred to 2ϩ oxaloacetate in the cytosol, the resulting malate is transported its role in phosphorylation reactions. (3) The presence of Mg into the matrix, and mitochondrial NADϩ is reduced to NADH. is essential to chlorophyll’s photochemical properties: light absorption and electron transfer. (b) (1) Enzymes catalyze 22. The citric acid cycle is stalled for lack of an acceptor of reversible reactions, so an isolated enzyme that can, under electrons from NADH. Pyruvate produced by glycolysis cannot certain laboratory conditions, catalyze removal of a phosphoryl enter the cycle as acetyl-CoA; accumulated pyruvate is group could probably, under different conditions (such as in transaminated to alanine and exported to the liver. cells), catalyze addition of a phosphoryl group. So it is plausible 23. Pyruvate dehydrogenase is located in mitochondria, that chlorophyll could be involved in the phosphorylation of glyceraldehyde 3-phosphate dehydrogenase in the cytosol. ADP. (2) There are two possible explanations: the chlorophyll The NAD pools are separated by the inner mitochondrial protein is a phosphatase only and does not catalyze ADP membrane. phosphorylation under cellular conditions, or the crude 24. Complete lack of glucokinase (two defective alleles) makes it preparation contains a contaminating phosphatase activity that impossible to carry out glycolysis at a sufficient rate to raise is unconnected to the photosynthetic reactions. (3) It is likely [ATP] to the threshold required for insulin secretion. that the preparation was contaminated with a nonphotosynthetic AbbreviatedSolutionsToProblems.indd Page AS-24 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-24 Abbreviated Solutions to Problems

phosphatase activity. (c) (1) This light inhibition is what one C4 plants, by fixing CO2 under conditions when rubisco prefers would expect if the chlorophyll protein catalyzed the reaction O2 as substrate, also contributes to setting atmospheric CO2/O2 ADP 1 Pi 1 light S ATP. Without light, the reverse reaction, a ratios. dephosphorylation, would be favored. In the presence of light, 9. (a) Without production of NADPH by the pentose phosphate energy is provided and the equilibrium would shift to the right, pathway, cells would be unable to synthesize lipids and other reducing the phosphatase activity. (2) This inhibition must be reduced products. (b) Without generation of ribulose an artifact of the isolation or assay methods. (3) It is unlikely 1,5-bisphosphate, the Calvin cycle is effectively blocked. that the crude preparation methods in use at the time preserved 10. In maize, CO2 is fixed by the C4 pathway elucidated by Hatch intact chloroplast membranes, so the inhibition must be an and Slack, in which PEP is carboxylated rapidly to oxaloacetate artifact. (d) (1) In the presence of light, ATP is synthesized and (some of which undergoes transamination to aspartate) and other phosphorylated intermediates are consumed. (2) In the reduced to malate. Only after subsequent decarboxylation does presence of light, glucose is produced and is metabolized by the CO2 enter the Calvin cycle. cellular respiration to produce ATP, with changes in the levels 11. Measure the rate of fixation of 14C carbon dioxide in the light of phosphorylated intermediates. (3) In the presence of light, (daytime) and the dark. Greater fixation in the dark identifies the ATP is produced and other phosphorylated intermediates are CAM plant. One could also determine the titratable acidity; acids consumed. (e) Light energy is used to produce ATP (as in the stored in the vacuole during the night can be quantified in this way. Emerson model) and is used to produce reducing power (as in the Rabinowitch model). (f) The approximate stoichiometry for 12. Isocitrate dehydrogenase reaction photophosphorylation (Chapter 19) is that 8 photons yield 2 13. Storage consumes 1 mol of ATP per mole of glucose 6-phosphate; NADPH and about 3 ATP. Two NADPH and 3 ATP are required this represents 3.3% of the total ATP available from glucose

to reduce 1 CO2 (Chapter 20). Thus, at a minimum, 8 photons 6-phosphate metabolism (i.e., the efficiency of storage is 96.7%).

are required per CO2 molecule reduced. This is in good 14. [PPi] is high in the cytosol because the cytosol lacks inorganic agreement with Rabinowitch’s value. (g) Because the energy of pyrophosphatase. light is used to produce both ATP and NADPH, each photon 15. (a) Low [Pi] in the cytosol and high [triose phosphate] in the absorbed contributes more than just 1 ATP for photosynthesis. chloroplast (b) High [triose phosphate] in the cytosol The process of energy extraction from light is more efficient 16. 3-Phosphoglycerate is the primary product of photosynthesis; [P ] than Rabinowitch supposed, and plenty of energy is available for i rises when light-driven synthesis of ATP from ADP and P slows. this process—even with red light. i 17. (a) Sucrose 1 (glucose)n S (glucose)nϩ1 1 fructose (b) Fructose generated in the synthesis of dextran is readily Chapter 20 imported and metabolized by the bacteria. 1. Within subcellular organelles, concentrations of specific 18. Species 1 is C4; species 2, C3. enzymes and metabolites are elevated; separate pools of 19. (a) In peripheral chloroplasts (b), (c) In central sphere cofactors and intermediates are maintained; regulatory 20. (a) By analogy to the oxygenic photosynthesis carried out by

mechanisms affect only one set of enzymes and pools. plants (H2O 1 CO2 S glucose 1 O2), the reaction would be 2. This observation suggests that ATP and NADPH are generated H2S 1 O2 1 CO2 S glucose 1 H2O 1 S. This is the sum of the S in the light and are essential for CO2 fixation; conversion stops reduction of CO2 by H2S (H2S 1 CO2 glucose 1 S) and the as the supply of ATP and NADPH becomes exhausted. energy input (H2S 1 O2 S S 1 H2O). (b) The H2S and CO2 are Furthermore, some enzymes are switched off in the dark. produced chemically in deep-sea sediments, but the O2, like the 3. X is 3-phosphoglycerate; Y is ribulose 1,5-bisphosphate. vast majority of O2 on Earth, is produced by photosynthesis, which is driven by light energy. (c) In the assay used by 4. Ribulose 5-phosphate kinase, fructose 1,6-bisphosphatase, Robinson et al., 3H labels the C-1 of ribulose 1,5-bisphosphate, sedoheptulose 1,7-bisphosphatase, and glyceraldehyde so reaction with CO yields one molecule of [3H]3- 3-phosphate dehydrogenase; all are activated by reduction of a 2 phosphoglycerate and one molecule of unlabeled critical disulfide bond to a pair of sulfhydryls; iodoacetate reacts 3-phosphoglycerate; reaction with O produces one molecule of irreversibly with free sulfhydryls. 2 [3H]2-phosphoglycolate and one molecule of unlabeled 5. To carry out the disulfide exchange reaction that activates the 3-phosphoglycerate. Thus the ratio of [3H]3-phosphoglycerate to Calvin cycle enzymes, thioredoxin needs both of its sulfhydryl [3H]2-phosphoglycolate equals the ratio of carboxylation to groups. oxygenation. (d) If the 3H labeled C-5, both oxygenation and 6. Reductive pentose phosphate pathway regenerates ribulose carboxylation would yield [3H]3-phosphoglycerate and it would 1,5-bisphosphate from triose phosphates produced during be impossible to distinguish which reaction had produced the photosynthesis. Oxidative pentose phosphate pathway provides labeled product; the reaction could not be used to measure V. NADPH for reductive biosynthesis and pentose phosphates for [CO ] 0.00038 nucleotide synthesis. (e) Substituting 2 5 5 0.0019 into [O2] 0.2 7. Both types of “respiration” occur in plants, consume O2, and produce CO . (Mitochondrial respiration also occurs in animals.) Vcarboxylation [CO ] 2 5V 2 gives Mitochondrial respiration occurs continuously; electrons derived Voxygenation [O2] from various fuels are passed through a chain of carriers in the Vcarboxylation inner mitochondrial membrane to O2. Photorespiration occurs in 5 (8.6)(0.0019) 5 0.016 chloroplasts, peroxisomes, and mitochondria. Photorespiration Voxygenation occurs during the daytime, when photosynthetic carbon fixation Therefore, the rate of oxygenation would be roughly 60 times is occurring; mitochondrial respiration occurs primarily at the rate of carboxylation! (f) If terrestrial plants had V 5 8.6, night, or during cloudy days. The path of electron flow in carboxylation would occur at a much lower rate than photorespiration is shown in Fig. 20–21; that for mitochondrial oxygenation. This would be extremely inefficient, so one would respiration, in Fig. 19–19. expect the rubisco of terrestrial plants to have an V 8. This hypothesis assumes directed evolution, or evolution with a substantially higher than 8.6. In fact, V values for land plants purpose—ideas not generally accepted by evolutionary vary between 10 and 250. Even with these values, the expected biologists. Other processes, such as burning fossil fuels and rate of the oxygenation reaction is still very high. (g) The global deforestation, affect the global atmospheric composition. rubisco reaction occurs with CO2 as a gas. At the same AbbreviatedSolutionsToProblems.indd Page AS-25 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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13 temperature, CO2 molecules diffuse more slowly than the 12. Methionine deficiency reduces the level of adoMet, which is 12 13 lighter CO2 molecules, and thus CO2 will enter the active site required for the de novo synthesis of phosphatidylcholine. The (and become incorporated into substrate) more slowly than salvage pathway does not employ adoMet, but uses available 12 CO2. (h) For the relationship to be truly symbiotic, the tube choline. Thus phosphatidylcholine can be synthesized even worms must be getting a substantial amount of their carbon when the diet is deficient in methionine, as long as choline is from the bacteria. The presence of rubisco in the endosymbionts available. simply shows that they are capable of chemosynthesis, not that 13. 14C label appears in three places in the activated isoprene: they are supplying the host with a significant fraction of its carbon. On the other hand, showing that the 13C:12C ratio in the 14 host is more similar to that in the endosymbiont than that in CH2 other marine animals strongly suggests that the tube worms are C 14CH CH getting the majority of their carbon from the bacteria. 2 2 14 CH3 Chapter 21 1. (a) The 16 carbons of palmitate are derived from 8 acetyl 14. (a) ATP (b) UDP-glucose (c) CDP-ethanolamine (d) UDP- groups of 8 acetyl-CoA molecules. The 14C-labeled acetyl-CoA galactose (e) fatty acyl–CoA (f) S-adenosylmethionine gives rise to malonyl-CoA labeled at C-1 and C-2. (b) The (g) malonyl-CoA (h) D3-isopentenyl pyrophosphate metabolic pool of malonyl-CoA, the source of all palmitate 15. Linoleate is required in the synthesis of prostaglandins. carbons except C-16 and C-15, does not become labeled with Animals are unable to transform oleate to linoleate, so linoleate small amounts of 14C-labeled acetyl-CoA. Hence, only [15,16-14C] is an essential fatty acid. Plants can transform oleate to palmitate is formed. linoleate, and they provide animals with the required linoleate 2. Both glucose and fructose are degraded to pyruvate in (see Fig. 21–12). glycolysis. Pyruvate is converted to acetyl-CoA by the pyruvate 16. The rate-determining step in the biosynthesis of cholesterol is dehydrogenase complex. Some of this acetyl-CoA enters the the synthesis of mevalonate, catalyzed by citric acid cycle, which produces reducing equivalents (NADH hydroxymethylglutaryl-CoA reductase. This enzyme is and NADPH). Mitochondrial electron transfer to O2 yields ATP. allosterically regulated by mevalonate and cholesterol

3. 8 Acetyl-CoA 1 15ATP 1 14NADPH 1 9H2O S derivatives. High intracellular [cholesterol] also reduces ϩ ϩ palmitate 1 8CoA 1 15ADP 1 15Pi 1 14NADP 1 2H transcription of the gene encoding HMG-CoA reductase. 4. (a) 3 deuteriums per palmitate; all located on C-16; all other 17. When cholesterol levels decline because of treatment with a two-carbon units are derived from unlabeled malonyl-CoA. statin, cells attempt to compensate by increasing expression of (b) 7 deuteriums per palmitate; located on all even-numbered the gene encoding HMG-CoA reductase. The statins are good carbons except C-16. competitive inhibitors of HMG-CoA reductase activity 5. By using the three-carbon unit malonyl-CoA, the activated form nonetheless and reduce overall production of cholesterol. of acetyl-CoA (recall that malonyl-CoA synthesis requires ATP), 18. Note: There are several plausible alternatives that a student metabolism is driven in the direction of fatty acid synthesis by might propose in the absence of a detailed knowledge of the

the exergonic release of CO2. literature on this enzyme. Thiolase reaction: Begins with 6. The rate-limiting step in fatty acid synthesis is carboxylation nucleophilic attack of an active-site Cys residue on the first O of acetyl-CoA, catalyzed by acetyl-CoA carboxylase. High acetyl-CoA substrate, displacing S-CoA and forming a [citrate] and [isocitrate] indicate that conditions are favorable covalent thioester link between Cys and the acetyl group. A for fatty acid synthesis: an active citric acid cycle is providing a base on the enzyme then extracts a proton from the methyl plentiful supply of ATP, reduced pyridine nucleotides, and group of the second acetyl-CoA, leaving a carbanion that attacks the carbonyl carbon of the thioester formed in the acetyl-CoA. Citrate stimulates (increases the Vmax of) acetyl- CoA carboxylase (a). Because citrate binds more tightly to the first step. The sulfhydryl of the Cys residue is displaced, filamentous form of the enzyme (the active form), high [citrate] creating the product acetoacetyl-CoA. HMG-CoA synthase drives the protomer Δ filament equilibrium in the direction of reaction: Begins in the same way, with a covalent thioester the active form (b). In contrast, palmitoyl-CoA (the end product link formed between the enzyme’s Cys residue and the of fatty acid synthesis) drives the equilibrium in the direction of acetyl group of acetyl-CoA, with displacement of the O O the inactive (protomer) form. Hence, when the end product of S-CoA. The S-CoA dissociates as CoA-SH, and fatty acid synthesis accumulates, the biosynthetic path slows. acetoacetyl-CoA binds to the enzyme. A proton is abstracted from the methyl group of the enzyme-linked acetyl, forming 7. (a) Acetyl-CoA 1 ATP 1 CoA S acetyl-CoA 1 ADP 1 (mit) (cyt) (cyt) a carbanion that attacks the ketone carbonyl of the P 1 CoA (b) 1 ATP per acetyl group (c) Yes i (mit) acetoacetyl-CoA substrate. The carbonyl is converted to a 8. The double bond in palmitoleate is introduced by an oxidation hydroxyl ion in this reaction, and this is protonated to catalyzed by fatty acyl–CoA desaturase, a mixed-function create OOH. The thioester link with the enzyme is then oxidase that requires O2 as a cosubstrate. cleaved hydrolytically to generate the HMG-CoA product.

9. 3 Palmitate 1 glycerol 1 7ATP 1 4H2O S HMG-CoA reductase reaction: Two successive hydride ions ϩ tripalmitin 1 7ADP 1 7Pi 1 7H derived from NADPH first displace the OS-CoA, and then 10. In adult rats, stored triacylglycerols are maintained at a steady- reduce the aldehyde to a hydroxyl group. state level through a balance of the rates of degradation and 19. Statins inhibit HMG-CoA reductase, an enzyme in the pathway to biosynthesis. Hence, the triacylglycerols of adipose (fat) tissue the synthesis of activated isoprenes, which are precursors of are constantly turned over, which explains the incorporation of cholesterol and a wide range of isoprenoids, including coenzyme 14C label from dietary glucose. Q (ubiquinone). Hence, statins might reduce the levels of 11. Net reaction: coenzyme Q available for mitochondrial respiration. Ubiquinone is obtained in the diet as well as by direct biosynthesis, but it is not Dihydroxyacetone phosphate 1 NADH 1 palmitate 1 oleate 1 yet clear how much is required and how well dietary sources can 3ATP 1 CTP 1 choline 1 4H2O S ϩ ϩ substitute for reduced synthesis. Reductions in the levels of phosphatidylcholine 1 NAD 1 2AMP 1 ADP 1 H 1 CMP 1 5Pi particular isoprenoids may account for some side effects of 7ATP per molecule of phosphatidylcholine statins. AbbreviatedSolutionsToProblems.indd Page AS-26 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-26 Abbreviated Solutions to Problems

20. (a) phosphate and formation of a double bond between the and O carbons. A rearrangement (beginning with proton abstraction H C 3 OH at the pyridoxal carbon adjacent to the substrate amino H3C CH3 CH3 CH3 nitrogen) moves the double bond between the and carbons, and converts the ketimine to the aldimine form of

CH3 CH3 H3C CH3 PLP. Attack of water at the carbon is then facilitated by the HO CH3 linked pyridoxal, followed by hydrolysis of the imine O link between PLP and the product, to generate threonine. Astaxanthin 4. In the mammalian route, toxic ammonium ions are transformed to glutamine, reducing toxic effects on the brain. (b) Head-to-head. There are two ways to look at this. First, the S ϩ “tail” of geranylgeranyl pyrophosphate has a branched dimethyl 5. Glucose 1 2CO2 1 2NH3 2 aspartate 1 2H 1 2H2O structure, as do both ends of phytoene. Second, no free OOH 6. The amino-terminal glutaminase domain is quite similar in all

is formed by the release of PPi, indicating that the two glutamine amidotransferases. A drug that targeted this active OO— P — P “heads” are linked to form phytoene. (c) Four site would probably inhibit many enzymes and thus be prone rounds of dehydrogenation convert four single bonds to double to producing many more side effects than a more specific bonds. (d) No. A count of single and double bonds in the inhibitor targeting the unique carboxyl-terminal synthetase reaction below shows that one double bond is replaced by two active site. single bonds—so, there is no net oxidation or reduction: 7. If phenylalanine hydroxylase is defective, the biosynthetic route to tyrosine is blocked and tyrosine must be obtained from the diet. 8. In adoMet synthesis, triphosphate is released from ATP. Lycopene (C-40) Hydrolysis of the triphosphate renders the reaction thermodynamically more favorable. bend ends around for cyclization 9. If the inhibition of glutamine synthase were not concerted, saturating concentrations of histidine would shut down the enzyme and cut off production of glutamine, which the bacterium needs to synthesize other products. 10. Folic acid is a precursor of tetrahydrofolate (see Fig. 18–16), cyclize required in the biosynthesis of glycine (see Fig. 22–14), a precursor of porphyrins. A folic acid deficiency therefore impairs hemoglobin synthesis. 11. For glycine auxotrophs: adenine and guanine; for glutamine auxotrophs: adenine, guanine, and cytosine; for aspartate -Carotene (C-40) auxotrophs: adenine, guanine, cytosine, and uridine. 12. (a) See Fig. 18–6, step 2, for the reaction mechanism of amino (e) Steps 1 through 3. The enzyme can convert IPP and acid racemization. The F atom of fluoroalanine is an excellent DMAP to geranylgeranyl pyrophosphate, but catalyzes no further leaving group. Fluoroalanine causes irreversible (covalent) reactions in the pathway, as confirmed by results with the other inhibition of alanine racemase. One plausible mechanism is (Nuc substrates. (f) Strains 1 through 4 lack crtE and have much denotes any nucleophilic amino acid side chain in the enzyme lower astaxanthin production than strains 5 through 8, all of active site): which overexpress crtE. Thus, overexpression of crtE leads to a Enz substantial increase in astaxanthin production. Wild-type E. coli : B Enz Enz H Nuc has some step 3 activity, but this conversion of farnesyl H HB Nuc pyrophosphate to geranylgeranyl pyrophosphate is strongly rate- Ϫ Ϫ Ϫ OOC C 2 FCH OOC C CH2 OOC C CH2 limiting. (g) IPP isomerase. Comparing strains 5 and 6 shows that FϪ N N N adding ispA, which catalyzes steps 1 and 2, has little effect on astaxanthin production, so these steps are not rate-limiting. CH CH CH However, comparing strains 5 and 7 shows that adding idi HO HO HO substantially increases astaxanthin production, so IPP isomerase P P P must be the rate-limiting step when crtE is overexpressed. (h) A ϩ ϩ ϩ CH N CH N CH N low (1) level, comparable to that of strains 5, 6, and 9. Without 3 H 3 H 3 H overexpression of idi, production of astaxanthin is limited by low IPP isomerase activity and the resulting limited supply of IPP. (b) Azaserine (see Fig. 22–51) is an analog of glutamine. The diazoacetyl group is highly reactive and forms covalent bonds Chapter 22 with nucleophiles at the active site of a glutamine 1. In their symbiotic relationship with the plant, bacteria supply amidotransferase. ammonium ion by reducing atmospheric nitrogen, which 13. (a) As shown in Fig. 18–16, p-aminobenzoate is a component of requires large quantities of ATP. N5,N10-methylenetetrahydrofolate, the cofactor involved in the

2. The transfer of nitrogen from NH3 to carbon skeletons can be transfer of one-carbon units. (b) In the presence of catalyzed by (1) glutamine synthetase and (2) glutamate sulfanilamide, a structural analog of p-aminobenzoate, bacteria dehydrogenase. The latter enzyme produces glutamate, the are unable to synthesize tetrahydrofolate, a cofactor necessary amino group donor in all transamination reactions, necessary for converting AICAR to FAICAR; thus AICAR accumulates. to the formation of amino acids for protein synthesis. (c) The competitive inhibition by sulfanilamide of the enzyme 3. A link between enzyme-bound PLP and the phosphohomoserine involved in tetrahydrofolate biosynthesis is overcome by the substrate is first formed, with rearrangement to generate addition of excess substrate (p-aminobenzoate). the ketimine at the carbon of the substrate. This activates the 14. The 14C-labeled orotate arises from the following pathway carbon for proton abstraction, leading to displacement of the (the first three steps are part of the citric acid cycle): AbbreviatedSolutionsToProblems.indd Page AS-27 15/10/12 7:21 AM user-F408 /Users/user-F408/Desktop

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Ϫ 14 14 14 14 Ϫ 15. Organisms do not store nucleotides to be used as fuel, and they OO C CH2 CH2 COO Succinate do not completely degrade them, but rather hydrolyze them to release the bases, which can be recovered in salvage pathways. The low C:N ratio of nucleotides makes them poor sources of energy. 16. Treatment with allopurinol has two consequences. (1) It inhibits ϪOO14CH conversion of hypoxanthine to uric acid, causing accumulation of hypoxanthine, which is more soluble and more readily 14 14 C C excreted; this alleviates the clinical problems associated with H 14COOϪ AMP degradation. (2) It inhibits conversion of guanine to uric Fumarate acid, causing accumulation of xanthine, which is less soluble than uric acid; this is the source of xanthine stones. Because the amount of GMP degradation is low relative to AMP degradation, the kidney damage caused by xanthine stones is less than that caused by untreated gout.

OH H 17. 5-Phosphoribosyl-1-pyrophosphate; this is the first NH3 acceptor in the purine biosynthetic pathway. ϪOO14C 14C 14C 14COOϪ 18. (a) The ␣-carboxyl group is removed and an OOH is added to H H the ␥ carbon. (b) BtrI has sequence homology with acyl carrier Malate proteins. The molecular weight of BtrI increases when incubated under conditions in which CoA could be added to the protein. Adding CoA to a Ser residue would replace an OOH (formula weight (FW) 17) with a 49-phosphopantetheine group (see Fig.

21–5). This group has the formula C11H21N2O7PS (FW 356). O H Thus, 11,182 2 17 1 356 5 12,151, which is very close to the ϪOO14C 14C 14C 14COOϪ observed Mr of 12,153. (c) The thioester could form with the ␣-carboxyl group. (d) In the most common reaction for H removing the ␣-carboxyl group of an amino acid (see Fig. 18–6c), Oxaloacetate the carboxyl group must be free. Furthermore, it is difficult to transamination imagine a decarboxylation reaction starting with a carboxyl group in its thioester form. (e) 12,240 2 12,281 5 41, close to ϩ the M of CO (44). Given that BtrK is probably a decarboxylase, NH r 2 3 its most likely structure is the decarboxylated form: Ϫ 14 14 14 14 Ϫ ϩ OO C C CH2 COO O H3N H S Aspartate BtrI

O (f) 12,370 2 12,240 5 130. Glutamic acid (C5H9NO4; Mr 147), 14 minus the OOH (FW 17) removed in the glutamylation reaction, C 14 ␥ ϩ Ϫ leaves a glutamyl group of FW 130; thus, -glutamylating the O CH2 H3N molecule above would add 130 to its M . BtrJ is capable of 14 r C C 14COOϪ ␥-glutamylating other substrates, so it may ␥-glutamylate the N OH structure above. The most likely site for this is the free amino H group, giving the following structure: O O

Ϫ O O O N ϩ H H 14 NH3 S C 14 N CH 2 BtrI 14 C C 14COOϪ OHN (g)

H ϩ ϩ NH3 NH3 CO2 ϪO O BtrJ ϪO O BtrK O O OϪ ATP ADP O S HH14 C 14 + BtrI N C BtrI 14 C C Glutamate 14COOϪ O N ATP ADP ϩ O H N H 3 BtrJ Orotate S

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AS-28 Abbreviated Solutions to Problems

H O activity. Phosphorylated intermediates cannot escape from the O2 2 O O cell, because the membrane is not permeable to charged O BtrO species, and glucose 6-phosphate is not exported on the glucose ϪO N H transporter. The liver, by contrast, must release the glucose ϩNH 3 S FMNH FMN necessary to maintain blood glucose level; glucose is formed 2 from glucose 6-phosphate and enters the bloodstream. BtrV BtrI 12. (a) Excessive uptake and use of blood glucose by the liver, leading to hypoglycemia; shutdown of amino acid and fatty acid ϩ NAD NADH catabolism (b) Little circulating fuel is available for ATP requirements. Brain damage results because glucose is the main source of fuel for the brain. Antibiotic O OOH 13. Thyroxine acts as an uncoupler of oxidative phosphorylation. Uncouplers lower the P/O ratio, and the tissue must increase O BtrG ϩ BtrH ϪO N respiration to meet the normal ATP demands. Thermogenesis ϩ H could also be due to the increased rate of ATP utilization by the NH3 S Glutamate ϩ BtrI thyroid-stimulated tissue, as increased ATP demands are met by BtrI increased oxidative phosphorylation and thus respiration. OH 14. Because prohormones are inactive, they can be stored in quantity in secretory granules. Rapid activation is achieved by ϩ O enzymatic cleavage in response to an appropriate signal. NH3 O 15. In animals, glucose can be synthesized from many precursors Antibiotic (see Fig. 14–16). In humans, the principal precursors are glycerol from triacylglycerols and glucogenic amino acids from protein. Chapter 23 16. The ob/ob mouse, which is initially obese, will lose weight. The 1. They are recognized by two different receptors, typically found OB/OB mouse will retain its normal body weight. in different cell types, and are coupled to different downstream 17. BMI 5 39.3. For BMI of 25, weight must be 75 kg; must lose effects. 43 kg 5 95 lbs. 2. Steady-state levels of ATP are maintained by phosphoryl group 18. Reduced insulin secretion. Valinomycin has the same effect as ϩ ϩ transfer to ADP from phosphocreatine. 1-Fluoro-2,4- opening the K channel, allowing K exit and consequent dinitrobenzene inhibits creatine kinase. hyperpolarization. 3. Ammonia is very toxic to nervous tissue, especially the brain. 19. The liver does not receive the insulin message and therefore

Excess NH3 is removed by transformation of glutamate to continues to have high levels of glucose 6-phosphatase and glutamine, which travels to the liver and is subsequently gluconeogenesis, increasing blood glucose both during a fast and transformed to urea. The additional glutamine arises from the after a glucose-containing meal. The elevated blood glucose transformation of glucose to -ketoglutarate, transamination of triggers insulin release from pancreatic cells, hence the high -ketoglutarate to glutamate, and conversion of glutamate to level of insulin in the blood. glutamine. 20. Some things to consider: What is the frequency of heart attack 4. Glucogenic amino acids are used to make glucose for the brain; attributable to the drug? How does this frequency compare with others are oxidized in mitochondria via the citric acid cycle. the number of individuals spared the long-term consequences of 5. From glucose, by the following route: Glucose S dihydroxyacetone type 2 diabetes? Are other, equally effective treatment options phosphate (in glycolysis); dihydroxyacetone phosphate 1 NADH 1 with fewer adverse effects available? Hϩ S glycerol 3-phosphate 1 NADϩ (glycerol 3-phosphate 21. Without intestinal glucosidase activity, absorption of glucose dehydrogenase reaction) from dietary glycogen and starch is reduced, blunting the usual 6. (a) Increased muscular activity increases the demand for ATP, rise in blood glucose after the meal. The undigested oligosaccharides are fermented by bacteria in the large intestine, which is met by increased O2 consumption. (b) After the sprint, lactate produced by anaerobic glycolysis is converted to glucose and the gases released cause intestinal discomfort. ϩ and glycogen, which requires ATP and therefore O2. 22. (a) Closing the ATP-gated K channel would depolarize the 7. Glucose is the primary fuel of the brain. TPP-dependent membrane, leading to increased insulin release. (b) Type 2 oxidative decarboxylation of pyruvate to acetyl-CoA is essential diabetes results from decreased sensitivity to insulin, not a to complete glucose metabolism. deficit of insulin production; increasing circulating insulin levels 8. 190 m will reduce the symptoms associated with this disease. (c) Individuals with type 1 diabetes have deficient pancreatic 9. (a) Inactivation provides a rapid means to change hormone cells, so glyburide will have no beneficial effect. (d) Iodine, like concentrations. (b) Insulin level is maintained by equal rates of chlorine (the atom it replaces in the labeled glyburide), is a synthesis and degradation. (c) Changes in the rate of release halogen, but it is a larger atom and has slightly different chemical from storage, rate of transport, and rate of conversion from properties. It is possible that the iodinated glyburide would not prohormone to active hormone. bind to SUR. If it bound to another molecule instead, the 10. Water-soluble hormones bind to receptors on the outer surface experiment would result in cloning of the gene for this other, of the cell, triggering the formation of a second messenger (e.g., incorrect protein. (e) Although a protein has been “purified,” the cAMP) inside the cell. Lipid-soluble hormones can pass through “purified” preparation might be a mixture of several proteins that the plasma membrane to act on target molecules or receptors co-purify under those experimental conditions. In this case, the directly. amino acid sequence could be that of a protein that co-purifies 11. (a) Heart and skeletal muscle lack glucose 6-phosphatase. Any with SUR. Using antibody binding to show that the peptide glucose 6-phosphate produced enters the glycolytic pathway, sequences are present in SUR excludes this possibility.

and under O2-deficient conditions is converted to lactate via (f) Although the cloned gene does encode the 25 amino acid pyruvate. (b) In a “fight or flight” situation, the concentration of sequence found in SUR, it could be a gene that, coincidentally, glycolytic precursors must be high in preparation for muscular encodes the same sequence in another protein. In this case, this AbbreviatedSolutionsToProblems.indd Page AS-29 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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other gene would most likely be expressed in different cells than 12. Centromere, telomeres, and an autonomous replicating the SUR gene. The mRNA hybridization results are consistent sequence or replication origin with the putative SUR cDNA actually encoding SUR. (g) The 13. The bacterial nucleoid is organized into domains approximately excess unlabeled glyburide competes with labeled glyburide for 10,000 bp long. Cleavage by a restriction enzyme relaxes the DNA the binding site on SUR. As a result, there is significantly less within a domain, but not outside the domain. Any gene in the binding of labeled glyburide, so little or no radioactivity is cleaved domain for which expression is affected by DNA topology detected in the 140 kDa protein. (h) In the absence of excess will be affected by the cleavage; genes outside the domain will not. unlabeled glyburide, labeled 140 kDa protein is found only in the 14. (a) The lower, faster-migrating band is negatively supercoiled presence of the putative SUR cDNA. Excess unlabeled glyburide plasmid DNA. The upper band is nicked, relaxed DNA. (b) DNA 125 competes with the labeled glyburide, and no I-labeled 140 kDa topoisomerase I relaxes the supercoiled DNA. The lower band protein is detected. This shows that the cDNA produces a will disappear, and all of the DNA will converge on the upper glyburide-binding protein of the same molecular weight as SUR— band. (c) DNA ligase produces little change in the pattern. strong evidence that the cloned gene encodes the SUR protein. Some minor additional bands may appear near the upper band, (i) Several additional steps are possible, such as: (1) Express due to the trapping of topoisomers not quite perfectly relaxed the putative SUR cDNA in CHO (Chinese hamster ovary) cells ϩ by the ligation reaction. (d) The upper band will disappear, and and show that the transformed cells have ATP-gated K channel all of the DNA will be in the lower band. The supercoiled DNA in activity. (2) Show that HIT cells with mutations in the putative ϩ the lower band may become even more supercoiled and migrate SUR gene lack ATP-gated K channel activity. (3) Show that somewhat faster. experimental animals or human patients with mutations in the 15. (a) When DNA ends are sealed to create a relaxed, closed circle, putative SUR gene are unable to secrete insulin. some DNA species are completely relaxed but others are trapped in slightly under- or overwound states. This gives rise to a Chapter 24 distribution of topoisomers centered on the most relaxed species. 1. 6.1 3 104 nm; 290 times longer than the T2 phage head (b) Positively supercoiled. (c) The DNA that is relaxed despite 2. The number of A residues does not equal the number of T residues, the addition of dye is DNA with one or both strands broken. DNA nor does the number of G equal the number of C, so the DNA is not isolation procedures inevitably introduce small numbers of strand a base-paired double helix; the M13 DNA is single-stranded. breaks in some of the closed-circular molecules. (d) Approximately 20.05. This is determined by simply comparing native DNA 3. M 5 3.8 3 108; length 5 200 m; Lk 5 55,200; Lk 5 51,900 r 0 with samples of known . In both gels, the native DNA migrates 4. The exons contain 3 bp/amino acid 3 192 amino acids 5 576 bp. most closely with the sample of 5 20.049. The remaining 864 bp are in introns, possibly in a leader or 16. 62 million (the genome refers to the haploid genetic content of signal sequence, and/or in other noncoding DNA. the cell; the cell is actually diploid, so the number of 5. 5,000 bp. (a) Doesn’t change; Lk cannot change without breaking nucleosomes is doubled). The number comes from 3.1 billion and re-forming the covalent backbone of the DNA. (b) Becomes base pairs divided by 200 base pairs per nucleosome (giving undefined; a circular DNA with a break in one strand has, by 15.5 million nucleosomes), multiplied by two copies of H2A per definition, no Lk. (c) Decreases; in the presence of ATP, gyrase nucleosome and again multiplied by 2 to account for the diploid underwinds DNA. (d) Doesn’t change; this assumes that neither state of the cell. The 62 million would double upon replication. of the DNA strands is broken in the heating process. 17. (a) In nondisjunction, one daughter cell and all of its 6. For Lk to remain unchanged, the topoisomerase must introduce descendants get two copies of the synthetic chromosome and the same number of positive and negative supercoils. are white; the other daughter cell and all of its descendants get 7. s 5 20.067; .70% probability no copies of the synthetic chromosome and are red. This gives 8. (a) Undefined; the strands of a nicked DNA could be separated rise to a half-white, half-red colony. (b) In chromosome loss, and thus have no Lk. (b) 476 (c) 476; the DNA is already relaxed, one daughter cell and all of its descendants get one copy of the so the topoisomerase does not cause a net change. (d) 460; gyrase synthetic chromosome and are pink; the other daughter and all plus ATP reduces the Lk in increments of 2. (e) 464; eukaryotic its descendants get no copies of the synthetic chromosome and type I topoisomerases increase the Lk of underwound or negatively are red. This gives rise to a half-pink, half-red colony. (c) The supercoiled DNA in increments of 1. (f) 460; nucleosome binding minimum functional centromere must be smaller than 0.63 kbp, does not break any DNA strands and thus cannot change Lk. since all fragments of this size or larger confer relative mitotic stability. (d) Telomeres are required to fully replicate only 9. A fundamental structural unit in chromatin repeats about every linear DNA; a circular molecule can replicate without them. 200 bp; the DNA is accessible to the nuclease only at 200 bp (e) The larger the chromosome, the more faithfully it is intervals. The brief treatment was insufficient to cleave the DNA segregated. The data show neither a minimum size below which at every accessible point, so a ladder of DNA bands is created in the synthetic chromosome is completely unstable, nor a which the DNA fragments are multiples of 200 bp. The thickness maximum size above which stability no longer changes. of the DNA bands suggests that the distance between cleavage sites varies somewhat. For instance, not all the fragments in the (f) 102 lowest band are exactly 200 bp long. 10 10. A right-handed helix has a positive Lk; a left-handed helix (such Synthetic chromosomes as Z-DNA) has a negative Lk. Decreasing the Lk of a closed 1 circular B-DNA by underwinding it facilitates formation of regions 10Ϫ1 of Z-DNA within certain sequences. (See Chapter 8, p. 291, for a Ϫ2 description of sequences that permit the formation of Z-DNA.) 10 Actual chromosomes 11. (a) Both strands must be covalently closed, and the molecule 10Ϫ3 must be either circular or constrained at both ends. (b) Formation log [error rate (%)] 10Ϫ4 of cruciforms, left-handed Z-DNA, plectonemic or solenoidal supercoils, and unwinding of the DNA are favored. (c) E. coli 10Ϫ5 DNA topoisomerase II or DNA gyrase. (d) It binds the DNA at a 500 100 150 200 250 300 point where it crosses on itself, cleaves both strands of one of the Length (kbp) crossing segments, passes the other segment through the break, As shown in the graph, even if the synthetic chromosomes were then reseals the break. The result is a change in Lk of 22. as long as the normal yeast chromosomes, they would not be as AbbreviatedSolutionsToProblems.indd Page AS-30 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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stable. This suggests that other, as yet undiscovered, elements 39-triphosphate, displacing pyrophosphate. Note that this are required for stability. mechanism would require the evolution of new metabolic pathways to supply the needed deoxynucleotide 39-triphosphates. Chapter 25 5 end Z O 1. In random, dispersive replication, in the second generation, all HO CH2 the DNAs would have the same density and would appear as a Z HO O H H single band, not the two bands observed in the Meselson-Stahl CH2 H H experiment. H H PPi 2. In this extension of the Meselson-Stahl experiment, after three H H O H 15 14 14 14 generations the molar ratio of N– N DNA to N– N DNA is ϪOPO OH H 2/6 5 0.33. O 5 P 5 end Y Y

3. (a) 4.42 3 10 turns; (b) 40 min. In cells dividing every : O O 20 min, a replicative cycle is initiated every 20 min, each cycle HO CH2 CH2 P beginning before the prior one is complete. (c) 2,000 to 5,000 H H H H Okazaki fragments. The fragments are 1,000 to 2,000 H H H H P nucleotides long and are firmly bound to the template strand by base pairing. Each fragment is quickly joined to the lagging O H O H strand, thus preserving the correct order of the fragments. ϪO P O ϪO P O 4. A 28.7%; G 21.3%; C 21.3%; T 28.7%. The DNA strand made O O from the template strand: A 32.7%; G 18.5%; C 24.1%; T 24.7%; X X O O the DNA strand made from the complementary template strand: CH2 CH2 A 24.7%; G 24.1%; C 18.5%; T 32.7%. It is assumed that the two H H H H template strands are replicated completely. H H H H 5. (a) No. Incorporation of 32P into DNA results from the O H O H synthesis of new DNA, which requires the presence of all four nucleotide precursors. (b) Yes. Although all four ϪOPO ϪOPO nucleotide precursors must be present for DNA synthesis, O O . only one of them has to be radioactive in order for . 3 end 3 end radioactivity to appear in the new DNA. (c) No. Radioactivity is incorporated only if the 32P label is in the phosphate; 7. The DNA polymerase contains a 39S59 exonuclease activity that DNA polymerase cleaves off pyrophosphate—i.e., the - and degrades DNA to produce [32P]dNMPs. The activity is not a -phosphate groups. 59S39 exonuclease, because the addition of unlabeled dNTPs 6. Mechanism 1: 39-OH of an incoming dNTP attacks the inhibits the production of [32P]dNMPs (polymerization activity phosphate of the triphosphate at the 59 end of the growing DNA would suppress a proofreading exonuclease but not an strand, displacing pyrophosphate. This mechanism uses normal exonuclease operating downstream of the polymerase). Addition dNTPs, and the growing end of the DNA always has a of pyrophosphate would generate [32P]dNTPs through reversal triphosphate on the 59 end. of the polymerase reaction. 5 end Z 8. Leading strand: Precursors: dATP, dGTP, dCTP, dTTP (also O P P P CH2 needs a template DNA strand and DNA primer); enzymes and other proteins: DNA gyrase, helicase, single-stranded DNA– H H Z H H binding protein, DNA polymerase III, topoisomerases, and O P P P CH2 pyrophosphatase. Lagging strand: Precursors: ATP, GTP, O H CTP, UTP, dATP, dGTP, dCTP, dTTP (also needs an RNA H H PPi H H ϪOPO primer); enzymes and other proteins: DNA gyrase, helicase, single-stranded DNA–binding protein, primase, DNA OH H O : Y polymerase III, DNA polymerase I, DNA ligase, topoisomerases, ϩ 5 end Y O and pyrophosphatase. NAD is also required as a cofactor for CH2 P P P CH O DNA ligase. 2 H H 9. Mutants with defective DNA ligase produce a DNA duplex in H H H H H H which one of the strands remains in pieces (as Okazaki O H fragments). When this duplex is denatured, sedimentation O H ϪO P O results in one fraction containing the intact single strand (the ϪO P O high molecular weight band) and one fraction containing the O X unspliced fragments (the low molecular weight band). O X O CH2 10. Watson-Crick base pairing between template and leading strand; CH O proofreading and removal of wrongly inserted nucleotides by the 2 H H H H H H 39-exonuclease activity of DNA polymerase III. Yes—perhaps. H H Because the factors ensuring fidelity of replication are operative O H in both the leading and the lagging strands, the lagging strand O H ϪOPO would probably be made with the same fidelity. However, the ϪOPO greater number of distinct chemical operations involved in O

. making the lagging strand might provide a greater opportunity O 3 end . for errors to arise. 3 end 11. 1,200 bp (600 in each direction) Mechanism 2: This uses a new type of precursor, nucleotide 39- 12. A small fraction (13 of 109 cells) of the histidine-requiring triphosphates. The growing end of the DNA strand has a 59-OH, mutants spontaneously undergo back-mutation and regain their which attacks the phosphate of an incoming deoxynucleotide capacity to synthesize histidine. 2-Aminoanthracene increases AbbreviatedSolutionsToProblems.indd Page AS-31 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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the rate of back-mutations about 1,800-fold and is therefore In the uvrϪ strain, the DNA is not repaired and the 3H level mutagenic. Since most carcinogens are mutagenic, increases as [3H]R7000 continues to react with the DNA. (e) All 2-aminoanthracene is probably carcinogenic. mutations listed in the table except APT to GqC show 13. Spontaneous deamination of 5-methylcytosine (see Fig. 8–30) significant increases over background. Each type of mutation produces thymine, and thus a G–T mismatched pair. These are results from a different type of interaction between R7000 and among the most common mismatches in the DNA of eukaryotes. DNA. Because different types of interactions are not equally The specialized repair system restores the GqC pair. likely (due to differences in reactivity, steric constraints, etc.), 14. (a) Ultraviolet irradiation produces pyrimidine dimers; in the resulting mutations occur with different frequencies. (f) No. q normal fibroblasts these are excised by cleavage of the damaged Only those that start with a G C base pair are explained by this P q P P strand by a special excinuclease. Thus the denatured single- model. Thus A T to C G and A T to T A must be due to stranded DNA contains the many fragments caused by the R7000 attaching to an A or a T. (g) R7000-G pairs with A. First, q q cleavage, and the average molecular weight is lowered. These R7000 adds to G C to give R7000-G C. (Compare this with fragments of single-stranded DNA are absent from the XPG what happens with the CH3-G in Fig. 25–27b.) If this is not P samples, as indicated by the unchanged average molecular repaired, one strand is replicated as R7000-G A, which is P weight. (b) The absence of fragments in the single-stranded repaired to T A. The other strand is wild-type. If the P DNA from the XPG cells after irradiation suggests the special replication produces R7000-G T, a similar pathway leads to an P excinuclease is defective or missing. A T base pair. (h) No. Compare data in the two tables, and keep in mind that different mutations occur at different 15. During homologous genetic recombination, a Holliday frequencies. intermediate may be formed almost anywhere within the two APT to CqG: moderate in both strains; but better repair in the paired, homologous chromosomes; the branch point of the ϩ intermediate can move extensively by branch migration. In site- uvr strain specific recombination, the Holliday intermediate is formed GqC to APT: moderate in both; no real difference between two specific sites, and branch migration is generally GqC to CPG: higher in uvrϩ; certainly less repair! restricted by heterologous sequences on either side of the GqC to TPA: high in both; no real difference recombination sites. APT to TPA: high in both; no real difference 16. (a) Points Y. (b) Points X. APT to GqC: low in both; no real difference 17. Once replication has proceeded from the origin to a point where Certain adducts may be more readily recognized by the repair one recombination site has been replicated but the other has apparatus than others and thus are repaired more rapidly and not, site-specific recombination not only inverts the DNA result in fewer mutations. between the recombination sites but also changes the direction of one replication fork relative to the other. The forks will chase each other around the DNA circle, generating many tandem Chapter 26 copies of the plasmid. The multimeric circle can be resolved to 1. (a) 60 to 100 s; (b) 500 to 900 nucleotides monomers by additional site-specific recombination events. 2. A single base error in DNA replication, if not corrected, would Origin Origin cause one of the two daughter cells, and all its progeny, to have 1 1 initiation of recombination at a mutated chromosome. A single base error in RNA transcription replication sites 1 and 2 (inversion) would not affect the chromosome; it would lead to formation of some defective copies of one protein, but because mRNAs turn 2 2 over rapidly, most copies of the protein would not be defective. Plasmid with Partially The progeny of this cell would be normal. recombination replicated 3. Normal posttranscriptional processing at the 39 end (cleavage sites 1 and 2 plasmid and polyadenylation) would be inhibited or blocked. 4. Because the template-strand RNA does not encode the enzymes Origin Origin needed to initiate viral infection, it would probably be inert or continued unidirectional simply degraded by cellular ribonucleases. Replication of the replication template-strand RNA and propagation of the virus could occur only if intact RNA replicase (RNA-dependent RNA polymerase) were introduced into the cell along with the template strand. Plasmid with Multimeric 5. AUGACCAUGAUUACG reoriented plasmid 6. (1) Use of a template strand of nucleic acid; (2) synthesis in the replication forks 59S39 direction; (3) use of nucleoside triphosphate substrates, with formation of a phosphodiester bond and displacement of

PPi. Polynucleotide phosphorylase forms phosphodiester bonds but differs in all other listed properties. 7. Generally two: one to cleave the phosphodiester bond at one intron-exon junction, the other to link the resulting free exon end to the exon at the other end of the intron. If the nucleophile 18. (a) Even in the absence of an added mutagen, background in the first step were water, this step would be a hydrolytic mutations occur due to radiation, cellular chemical reactions, event and only one transesterification step would be required to and so forth. (b) If the DNA is sufficiently damaged, a complete the splicing process. substantial fraction of gene products are nonfunctional and the 8. Many snoRNAs, required for rRNA modification reactions, are cell is nonviable. (c) Cells with reduced DNA repair capability encoded in introns. If splicing does not occur, snoRNAs are not are more sensitive to mutagens. Because they less readily repair produced. Ϫ lesions caused by R7000, uvr bacteria have an increased 9. These enzymes lack a 39S59 proofreading exonuclease and have mutation rate and increased chance of lethal effects. (d) In the a high error rate; the likelihood of a replication error that would ϩ uvr strain, the excision-repair system removes DNA bases with inactivate the virus is much less in a small genome than in a attached [3H]R7000, decreasing the 3H in these cells over time. large one. AbbreviatedSolutionsToProblems.indd Page AS-32 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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10. (a) 432 5 1.8 3 1019 (b) 0.006% (c) For the “unnatural selection” 13. (a) 384 nucleotide pairs (b) 1,620 nucleotide pairs (c) Most step, use a chromatographic resin with a bound molecule that is a of the nucleotides are untranslated regions at the 39 and 59 transition-state analog of the ester hydrolysis reaction. ends of the mRNA. Also, most mRNAs code for a signal 11. Though RNA synthesis is quickly halted by -amanitin toxin, it sequence (Chapter 27) in their protein products, which is takes several days for the critical mRNAs and the proteins in the eventually cleaved off to produce the mature and functional liver to degrade, causing liver dysfunction and death. protein. 12. (a) After lysis of the cells and partial purification of the 14. (a) cDNA is produced by reverse transcription of mRNA; contents, the protein extract could be subjected to isoelectric thus, the mRNA sequence is probably CGG. Because the focusing. The subunit could be detected by an antibody-based genomic DNA transcribed to make the mRNA has the sequence assay. The difference in amino acid residues between the normal CAG, the primary transcript most likely has CAG, which is subunit and the mutated form (i.e., the different charges on posttranscriptionally modified to CGG. (b) The unedited the amino acids) would alter the electrophoretic mobility of the mRNA sequence is the same as that of the DNA (except for mutant protein in an isoelectric focusing gel, relative to the U replacing T). Unedited mRNA has the sequence (* indicates protein from a nonresistant strain. (b) Direct DNA sequencing site of editing) (by the Sanger method).

* (5) GUCUCUGGUUUUCCUUGGGUGCCUUUAUGCAGCAAGGAUGCGAUAUUUCGCCAAG (3) In step 1, primer 1 anneals as shown: * (5) GUCUCUGGUUUUCCUUGGGUGCCUUUAUGCAGCAAGGAUGCGAUAUUUCGCCAAG (3)

Primer 1: (3)CGTTCCTACGCTATAAAGCGGTTC(5)

cDNA (underlined) is synthesized from right to left: * (5) GUCUCUGGUUUUCCUUGGGUGCCUUUAUGCAGCAAGGAUGCGAUAUUUCGCCAAG (3)

(3) CAGAGACCAAAAGGAACCCACGGAAATACGTCGTTCCTACGCTATAAAGCGGTTC(5)

Then step 2 yields just the cDNA: * (3) CAGAGACCAAAAGGAACCCACGGAAATACGTCGTTCCTACGCTATAAAGCGGTTC(5)

In step 3, primer 2 anneals to the cDNA: Primer 2: (5)CCTTGGGTGCCTTTA(3)

(3) CAGAGACCAAAAGGAACCCACGGAAATACGTCGTTCCTACGCTATAAAGCGGTTC (5) * DNA polymerase adds nucleotides to the 39 end of this primer. Moving from left to right, it inserts T, G, C, and A. However, because the A from ddATP lacks the 39 OOH needed to attach the next nucleotide, the chain is not elongated past this point. This A is shown in italic; the new DNA is underlined: Primer 2: (5)CCTTGGGTGCCTTTATGCA

(3) CAGAGACCAAAAGGAACCCACGGAAATACGTCGTTCCTACGCTATAAAGCGGTTC(5) * This yields a 19 nucleotide fragment for the unedited transcript. In the edited transcript, the *A is changed to G; in the cDNA this corresponds to C. At the start of step 3: Primer 2: (5)CCTTGGGTGCCTTTA(3)

(3) CAGAGACCAAAAGGAACCCACGGAAATACGCCGTTCCTACGCTATAAAGCGGTTC(5) * In this case, DNA polymerase can elongate past the edited base and will stop at the next T in the cDNA. The dideoxy A is italic; the new DNA is underlined: Primer 2: (5)CCTTGGGTGCCTTTATGCGGCA

(3) CAGAGACCAAAAGGAACCCACGGAAATACGCCGTTCCTACGCTATAAAGCGGTTC(5)

This gives the 22 nucleotide product. (c) Treatments types of [32P]NTPs, none of the products would have been (proteases, heat) known to disrupt protein function inhibit the labeled. (e) Because only an A is being edited, only the fate of editing activity, whereas treatments (nuclease) that do not any A in the sequence is of interest. (f) Given that only ATP affect proteins have little or no effect on editing. A key was labeled, if the entire nucleotide were removed, all weakness of this argument is that the protein-disrupting radioactivity would have been removed from the mRNA, so treatments do not completely abolish editing. There could be only unmodified [32P]AMP would be present on the some background editing or degradation of the mRNA even chromatography plate. (g) If the base were removed and without the enzyme, or some of the enzyme might survive the replaced, one would expect to see only [3H]AMP. The presence treatments. (d) Only the phosphate of NTPs is incorporated of [3H]IMP indicates that the A to I change occurs without into polynucleotides. If the researchers had used the other removal of H at positions 2 and 8. The most likely mechanism AbbreviatedSolutionsToProblems.indd Page AS-33 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

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is chemical modification of A to I by hydrolytic deamination 10. (59)AUGAUAUUGCUAUCUUGGACU (see Fig. 22–36). (h) CAG is changed to CIG. This codon is Changes: C C AU U C C read as CGG. U C A A G G G Chapter 27 14 of 63 possible one-base changes would result in no coding change. 1. (a) Gly–Gln–Ser–Leu–Leu–Ile (b) Leu–Asp–Ala–Pro 11. The two DNA codons for Glu are GAA and GAG, and the four (c) His–Asp–Ala–Cys–Cys–Tyr (d) Met–Asp–Glu in eukaryotes; DNA codons for Val are GTT, GTC, GTA, and GTG. A single base fMet–Asp–Glu in bacteria change in GAA to form GTA or in GAG to form GTG could 2. UUAAUGUAU, UUGAUGUAU, CUUAUGUAU, CUCAUGUAU, account for the Glu S Val replacement in sickle-cell CUAAUGUAU, CUGAUGUAU, UUAAUGUAC, UUGAUGUAC, hemoglobin. Much less likely are two-base changes, from GAA to CUUAUGUAC, CUCAUGUAC, CUAAUGUAC, CUGAUGUAC GTG, GTT, or GTC; and from GAG to GTA, GTT, or GTC. 3. No. Because nearly all the amino acids have more than one 12. Isoleucine is similar in structure to several other amino acids, codon (e.g., Leu has six), any given polypeptide can be coded particularly valine. Distinguishing between valine and isoleucine for by a number of different base sequences. However, some in the aminoacylation process requires the second filter of a amino acids are encoded by only one codon and those with proofreading function. Histidine has a structure unlike that of multiple codons often share the same nucleotide at two of the any other amino acid, and this structure provides opportunities three positions, so certain parts of the mRNA sequence for binding specificity adequate to ensure accurate encoding a protein of known amino acid sequence can be aminoacylation of the cognate tRNA. predicted with high certainty. 13. (a) The Ala-tRNA synthetase recognizes the G3–U70 base pair in 4. (a) (59)CGACGGCGCGAAGUCAGGGGUGUUAAG(39) the amino acid arm of tRNAAla. (b) The mutant tRNAAla would (b) Arg–Arg–Arg–Glu–Val–Arg–Gly–Val–Lys insert Ala residues at codons encoding Pro. (c) A mutation that (c) No. The complementary antiparallel strands in double- might have similar effects is an alteration in tRNAPro that helical DNA do not have the same base sequence in the 59S39 allowed it to be recognized and aminoacylated by Ala-tRNA direction. RNA is transcribed from only one specific strand of synthetase. (d) Most of the proteins in the cell would be duplex DNA. The RNA polymerase must therefore recognize and inactivated, so these would be lethal mutations and hence never bind to the correct strand. observed. This represents a powerful selective pressure for 5. There are two tRNAs for methionine: tRNAfMet, which is the maintaining the genetic code. initiating tRNA, and tRNAMet, which can insert a Met residue in 14. IF-2: The 70S ribosome would form, but initiation factors would interior positions in a polypeptide. Only fMet-tRNAfMet is not be released and elongation could not start. EF-Tu: The recognized by the initiation factor IF-2 and is aligned with the second aminoacyl-tRNA would bind to the ribosomal A site, but initiating AUG positioned at the ribosomal P site in the initiation no peptide bond would form. EF-G: The first peptide bond complex. AUG codons in the interior of the mRNA can bind and would form, but the ribosome would not move along the mRNA incorporate only Met-tRNAMet. to vacate the A site for binding of a new EF-Tu–tRNA. 6. Allow polynucleotide phosphorylase to act on a mixture of UDP 15. The amino acid most recently added to a growing polypeptide and CDP in which UDP has, say, five times the concentration of chain is the only one covalently attached to a tRNA and thus CDP. The result would be a synthetic RNA polymer with many is the only link between the polypeptide and the mRNA UUU triplets (coding for Phe), a smaller number of UUC (Phe), encoding it. A proofreading activity would sever this link, UCU (Ser), and CUU (Leu), a much smaller number of UCC halting synthesis of the polypeptide and releasing it from the (Ser), CUC (Leu), and CCU (Pro), and the smallest number of mRNA. CCC (Pro). 16. The protein would be directed into the ER, and from there the 7. A minimum of 583 ATP equivalents (based on 4 per amino acid targeting would depend on additional signals. SRP binds the residue added, except that there are only 145 translocation amino-terminal signal early in protein synthesis and directs the steps). Correction of each error requires 2 ATP equivalents. For nascent polypeptide and ribosome to receptors in the ER. glycogen synthesis, 292 ATP equivalents. The extra energy cost Because the protein is translocated into the lumen of the ER as for -globin synthesis reflects the cost of the information it is synthesized, the NLS is never accessible to the proteins content of the protein. At least 20 activating enzymes, 70 involved in nuclear targeting. ribosomal proteins, 4 rRNAs, 32 or more tRNAs, an mRNA, and 17. Trigger factor is a molecular chaperone that stabilizes an 10 or more auxiliary enzymes must be made by the eukaryotic unfolded and translocation-competent conformation of cell in order to synthesize a protein from amino acids. The ProOmpA. S synthesis of an ( 1 4) chain of glycogen from glucose requires 18. DNA with a minimum of 5,784 bp; some of the coding sequences only 4 or 5 enzymes (Chapter 15). must be nested or overlapping. 8. 19. (a) The helices associate through hydrophobic and van der Glycine codons Anticodons Waals interactions. (b) R groups 3, 6, 7, and 10 extend to the left; 1, 2, 4, 5, 8, and 9 extend to the right. (c) One possible (59)GGU (59)ACC, GCC, ICC sequence is (59)GGC (59)GCC, ICC 123 4 5 6 78 910 (59)GGA (59)UCC, ICC N C (59)GGG (59)CCC, UCC –Phe–Ile–Glu–Val–Met–Asn–Ser–Ala–Phe–Gln– (d) One possible DNA sequence for the amino acid sequence in (a) The 39 and middle position (b) Pairings with anticodons (c) is (59)GCC, ICC, and UCC (c) Pairings with anticodons (59)ACC and CCC Nontemplate strand 9. (a), (c), (e), and (g) only; (b), (d), and (f) cannot be the result (5)TTTATTGAAGTAATGAATAGTGCATTCC AG(3) of single-base mutations: (b) and (f) would require substitutions of two bases, and (d) would require substitutions of all three (3)AAATAACTTCATTACTTATCACGTAAGGTC(5) bases. Template strand AbbreviatedSolutionsToProblems.indd Page AS-34 05/10/12 11:00 AM user-F408 /Users/user-F408/Desktop

AS-34 Abbreviated Solutions to Problems

(e) Phe, Leu, Ile, Met, and Val. All are hydrophobic, but the set 11. does not include all the hydrophobic amino acids; Trp, Pro, Ala, Gal4 protein and Gly are missing. (f) Tyr, His, Gln, Asn, Lys, Asp, and Glu. All of these are hydrophilic, although Tyr is less hydrophilic than the others. The set does not include all the hydrophilic amino acids; Gal4 DNA-binding domain Gal4 activator domain Ser, Thr, and Arg are missing. (g) Omitting T from the mixture excludes codons starting or ending with T—thus excluding Tyr, Engineered protein which is not very hydrophilic, and, more importantly, excluding the two possible stop codons (TAA and TAG). No other amino Lac repressor DNA-binding domain Gal4 activator domain acids in the NAN set are excluded by omitting T. (h) Misfolded proteins are often degraded in the cell. Therefore, if a synthetic The engineered protein cannot bind to the Gal4 binding site in gene has produced a protein that forms a band on the SDS gel, it the GAL gene (UAS ) because it lacks the Gal4 DNA-binding is likely that this protein is folded properly. (i) Protein folding G domain. Modify the Gal4p DNA binding site to give it the depends on more than hydrophobic and van der Waals nucleotide sequence to which the Lac repressor normally binds interactions. There are many reasons why a synthesized random- (using methods described in Chapter 9). sequence protein might not fold into the four-helix structure. For example, hydrogen bonds between hydrophilic side chains could 12. Methylamine. The reaction proceeds with attack of water on the disrupt the structure. Also, not all sequences have an equal guanidinium carbon of the modified arginine. propensity to form an helix. 13. The bcd mRNA needed for development is contributed to the egg by the mother. The egg develops normally even if its Chapter 28 genotype is bcdϪ/bcdϪ, as long as the mother has one normal Ϫ 1. (a) Tryptophan synthase levels remain high in spite of the bcd gene and the bcd allele is recessive. However, the adult Ϫ Ϫ presence of tryptophan. (b) Levels again remain high. bcd /bcd female will be sterile because she has no normal bcd (c) Levels rapidly decrease, preventing wasteful synthesis of mRNA to contribute to her own eggs. tryptophan. 14. (a) For 10% expression (90% repression), 10% of the repressor 2. The E. coli cells will produce -galactosidase when they are has bound inducer and 90% is free and available to bind the subjected to high levels of a DNA-damaging agent, such as UV operator. The calculation uses Eqn 5–8 (p. 161), with 5 0.1 Ϫ4 light. Under such conditions, RecA binds to single-stranded and Kd 5 10 M. chromosomal DNA and facilitates the autocatalytic cleavage of [IPTG] [IPTG] the LexA repressor, releasing LexA from its binding site and 5 5 [IPTG] 1 K 24 allowing transcription of downstream genes. d [IPTG] 1 10 M

[IPTG] Ϫ5 Ϫ5 3. (a) Constitutive, low-level expression of the operon; most 0.1 5 so 0.9 [IPTG] 5 10 [IPTG] 5 1.1 3 10 M 24 or mutations in the operator would make the repressor less likely [IPTG] 1 10 M to bind. (b) Either constitutive expression, as in (a), or For 90% expression, 90% of the repressor has bound inducer, so constant repression, if the mutation destroyed the capability to 5 0.9. Entering the values for and Kd in Eqn 5–8 gives [IPTG] Ϫ4 bind to lactose and related compounds and hence the response 5 9 3 10 M. Thus, gene expression varies 10-fold over a roughly to inducers. (c) Either increased or decreased expression of 10-fold [IPTG] range. (b) You would expect the protein levels to the operon (under conditions in which it is induced), be low before induction, rise during induction, and then decay as depending on whether the mutation made the promoter more synthesis stops and the proteins are degraded. (c) As shown in or less similar, respectively, to the consensus E. coli promoter. (a), the lac operon has more levels of expression than just on or 4. 7,000 copies off; thus it does not have characteristic A. As shown in (b), Ϫ9 5 5. 8 3 10 M, about 10 times greater than the dissociation expression of the lac operon subsides once the inducer is constant. With 10 copies of active repressor in the cell, the removed; thus it lacks characteristic B. (d) GFP-on: repts and ts operator site is always bound by the repressor molecule. GFP are expressed at high levels; rep represses OP, so no LacI 6. (a)–(e) Each condition decreases expression of lac operon protein is produced. GFP-off: LacI is expressed at a high level; ts genes. LacI represses OPlac, so rep and GFP are not produced. (e) IPTG treatment switches the system from GFP-off to GFP-on. 7. (a) Less attenuation of transcription. The ribosome completing IPTG has an effect only when LacI is present, so affects only the the translation of sequence 1 would no longer overlap and block GFP-off state. Adding IPTG relieves the repression of OP , sequence 2; sequence 2 would always be available to pair with lac allowing high-level expression of repts, which turns off expression sequence 3, preventing formation of the attenuator structure. of LacI, and high-level expression of GFP. (f) Heat treatment (b) More attenuation of transcription. Sequence 2 would pair switches the system from GFP-on to GFP-off. Heat has an effect less efficiently with sequence 3; the attenuator structure would only when repts is present, so affects only the GFP-on state. Heat be formed more often, even when sequence 2 was not blocked ts inactivates rep and relieves the repression of OP␭, allowing high- by a ribosome. (c) No attenuation of transcription. The only level expression of LacI. LacI then acts at OP to repress regulation would be that afforded by the Trp repressor. lac synthesis of repts and GFP. (g) Characteristic A: The system is (d) Attenuation loses its sensitivity to Trp tRNA. It might not stable in the intermediate state. At some point, one repressor become sensitive to His tRNA. (e) Attenuation would rarely, if will act more strongly than the other due to chance fluctuations ever, occur. Sequences 2 and 3 always block formation of the in expression; this shuts off expression of the other repressor and attenuator. (f) Constant attenuation of transcription. Attenuator locks the system in one state. Characteristic B: Once one always forms, regardless of the availability of tryptophan. repressor is expressed, it prevents the synthesis of the other; thus 8. Induction of the SOS response could not occur, making the cells the system remains in one state even after the switching stimulus more sensitive to high levels of DNA damage. has been removed. (h) At no time does any cell express an 9. Each Salmonella cell would have flagella made up of both types intermediate level of GFP—this is a confirmation of characteristic of flagellar protein, and the cell would be vulnerable to A. At the intermediate concentration (X) of inducer, some cells antibodies generated in response to either protein. have switched to GFP-on while others have not yet made the 10. A dissociable factor necessary for activity (e.g., a specificity switch and remain in the GFP-off state; none are in between. The factor similar to the s subunit of the E. coli enzyme) may have bimodal distribution of expression levels at [IPTG] 5 X is caused been lost during purification of the polymerase. by the mixed population of GFP-on and GFP-off cells. BMGlossary.indd Page G-1 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary

a that have binding sites for two or more cellular amino acids: ␣-Amino–substituted carboxylic components and serve to bring those compo- ABC transporters: Plasma membrane acids, the building blocks of proteins. nents together. proteins with sequences that make up ATP- aminoacyl-tRNA: An aminoacyl ester of a binding cassettes; serve to transport a large adenosine 39,59-cyclic monophosphate: tRNA. variety of substrates, including inorganic ions, See cyclic AMP. aminoacyl-tRNA synthetases: Enzymes lipids, and nonpolar drugs, out of the cell, S-adenosylmethionine (adoMet): An that catalyze synthesis of an aminoacyl-tRNA using ATP as the energy source. enzymatic cofactor involved in methyl group at the expense of ATP energy. absolute confi guration: The confi guration transfers. amino-terminal residue: The only amino of four different substituent groups around an adipocyte: An animal cell specialized for the acid residue in a polypeptide chain with a free asymmetric carbon atom, in relation to D- and storage of fats (triacylglycerols). ␣-amino group; defi nes the amino terminus of L-glyceraldehyde. adipose tissue: Connective tissue specialized the polypeptide. absorption: Transport of the products of diges- for the storage of large amounts of triacyl- aminotransferases: Enzymes that catalyze tion from the intestinal tract into the blood. glycerols. See also brown adipose tissue; white the transfer of amino groups from ␣-amino to acceptor control: Regulation of the rate of adipose tissue. ␣-keto acids; also called transaminases. respiration by the availability of ADP as phos- ADP (adenosine diphosphate): A ribonu- ammonotelic: Excreting excess nitrogen in phate group acceptor. cleoside 59-diphosphate serving as phosphate the form of ammonia. accessory pigments: Visible light–absorbing group acceptor in the cell energy cycle. AMP-activated protein kinase (AMPK): pigments (carotenoids, xanthophylls, and phy- aerobe: An organism that lives in air and uses A protein kinase activated by 59-adenosine cobilins) in plants and photosynthetic bacteria oxygen as the terminal electron acceptor in monophosphate (AMP). AMPK action gener- that complement chlorophylls in trapping respiration. ally shifts metabolism away from biosynthesis energy from sunlight. aerobic: Requiring or occurring in the presence toward energy production. acid dissociation constant: The dissociation of oxygen. amphibolic pathway: A metabolic pathway constant (K ) of an acid, describing its disso- a agonist: A compound, typically a hormone or used in both catabolism and anabolism. ciation into its conjugate base and a proton. neurotransmitter, that elicits a physiological amphipathic: Containing both polar and acidosis: A metabolic condition in which the response when it binds to its specifi c receptor. nonpolar domains. capacity of the body to buffer Hϩ is diminished; amphitropic proteins: Proteins that associ- usually accompanied by decreased blood pH. alcohol fermentation: See ethanol fermentation. ate reversibly with the membrane and thus actin: A protein that makes up the thin fi la- can be found in the cytosol, in the membrane, aldose: A simple sugar in which the carbonyl ments of muscle; also an important component or in both places. of the cytoskeleton of many eukaryotic cells. carbon atom is an aldehyde; that is, the car- bonyl carbon is at one end of the carbon chain. ampholyte: A substance that can act as either action spectrum: A plot of the effi ciency of a base or an acid. light at promoting a light-dependent pro- alkalosis: A metabolic condition in which the Ϫ amphoteric: Capable of donating and accept- cess such as photosynthesis as a function of capacity of the body to buffer OH is dimin- ing protons, thus able to serve as an acid or a wavelength. ished; usually accompanied by an increase in blood pH. base. activation energy (DG‡): The amount of AMPK: See AMP-activated protein kinase. energy (in joules) required to convert all the allosteric enzyme: A regulatory enzyme with molecules in 1 mol of a reacting substance catalytic activity modulated by the noncova- amyloidoses: A variety of progressive condi- from the ground state to the transition state. lent binding of a specifi c metabolite at a site tions characterized by abnormal deposits of misfolded proteins in one or more organs or activator: (1) A DNA-binding protein that other than the active site. tissues. positively regulates the expression of one allosteric protein: A protein (generally with or more genes; that is, transcription rates multiple subunits) with multiple ligand-binding anabolism: The phase of intermediary me- increase when an activator is bound to the sites, such that ligand binding at one site tabolism concerned with the energy-requiring DNA. (2) A positive modulator of an allosteric affects ligand binding at another. biosynthesis of cell components from smaller enzyme. allosteric site: The specifi c site on the sur- precursors. active site: The region of an enzyme surface face of an allosteric enzyme molecule to which anaerobe: An organism that lives without that binds the substrate molecule and catalyti- the modulator or effector molecule is bound. oxygen. Obligate anaerobes die when exposed cally transforms it; also known as the catalytic ␣ helix: A helical conformation of a polypep- to oxygen. site. tide chain, usually right-handed, with maximal anaerobic: Occurring in the absence of air or active transport: Energy-requiring transport intrachain hydrogen bonding; one of the most oxygen. of a solute across a membrane in the direction common secondary structures in proteins. analyte: A molecule to be analyzed by mass of increasing concentration. ␣ oxidation: An alternative path for the oxi- spectrometry. activity: The true thermodynamic activity or dation of ␤-methyl fatty acids in peroxisomes. anammox: Anaerobic oxidation of ammonia to potential of a substance, as distinct from its Ames test: A simple bacterial test for car- N2, using nitrite as electron acceptor; carried molar concentration. cinogenicity, based on the assumption that out by specialized chemolithotrophic bacteria. acyl phosphate: Any molecule with the carcinogens are mutagens. anaplerotic reaction: An enzyme-catalyzed general chemical form ᎏ ᎏ ᎏ 2Ϫ . R CB O OPO3 amino acid activation: ATP-dependent reaction that can replenish the supply of inter-

O enzymatic esterifi cation of the carboxyl group mediates in the citric acid cycle. Ϫ adaptor proteins: Signaling proteins, gener- of an amino acid to the 39-hydroxyl group of angstrom (Å): A unit of length (10 8 cm) ally without their own enzymatic activities, its corresponding tRNA. used to indicate molecular dimensions. G-1 BMGlossary.indd Page G-2 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-2 Glossary

anhydride: The product of the condensation groups and thus may exist in two different tions at the ␤-carbon atom; as distinct from ␻ of two carboxyl or phosphate groups in which tetrahedral confi gurations. oxidation. the elements of water are eliminated to form a ATP (adenosine triphosphate): A ribonu- ␤ turn: A type of protein secondary structure compound with the general structure cleoside 59-triphosphate functioning as a phos- consisting of four amino acid residues arranged RᎏXᎏOᎏXᎏR, where X is either carbon B B phate group donor in the cellular energy cycle; in a tight turn so that the polypeptide turns O O carries chemical energy between metabolic back on itself. or phosphorus. pathways by serving as a shared intermediate bilayer: A double layer of oriented amphipathic anion-exchange resin: A polymeric resin coupling endergonic and exergonic reactions. lipid molecules, forming the basic structure of with fi xed cationic groups, used in the chro- ATPase: An enzyme that hydrolyzes ATP to biological membranes. The hydrocarbon tails matographic separation of anions. yield ADP and phosphate, usually coupled to a face inward to form a continuous nonpolar anomeric carbon: The carbon atom in a process requiring energy. phase. sugar at the new stereocenter formed when a ATP synthase: An enzyme complex that bile acids: Polar derivatives of cholesterol, sugar cyclizes to form a hemiacetal. This is the forms ATP from ADP and phosphate during secreted by the liver into the intestine, that carbonyl carbon of aldehydes and ketones. oxidative phosphorylation in the inner mito- serve to emulsify dietary fats, facilitating lipase anomers: Two stereoisomers of a given sugar chondrial membrane or the bacterial plasma action on them. that differ only in the confi guration about the membrane, and during photophosphorylation bile salts: Amphipathic steroid derivatives carbonyl (anomeric) carbon atom. in chloroplasts. with detergent properties, participating in antagonist: A compound that interferes with attenuator: An RNA sequence involved in digestion and absorption of lipids. the physiological action of another substance regulating the expression of certain genes; binding energy: The energy derived from (the agonist), usually at a hormone or neu- functions as a transcription terminator. noncovalent interactions between enzyme and rotransmitter receptor. autophagy: Catabolic lysosomal degradation substrate or receptor and ligand. antibiotic: One of many different organic of cellular proteins and other components. binding site: The crevice or pocket on a compounds that are formed and secreted by autophosphorylation: Strictly, the phos- protein in which a ligand binds. various species of microorganisms and plants, phorylation of an amino acid residue in a bioassay: A method for measuring the amount are toxic to other species, and presumably protein that is catalyzed by the same protein of a biologically active substance (such as a have a defensive function. molecule; often extended to include phos- hormone) in a sample by quantifying the bio- antibody: A defense protein synthesized by phorylation of one subunit of a homodimer by logical response to aliquots of that sample. the immune system of vertebrates. See also the other subunit. bioinformatics: The computerized analysis immunoglobulin. autotroph: An organism that can synthesize of biological data, using methods derived from anticodon: A specifi c sequence of three its own complex molecules from very simple statistics, linguistics, mathematics, chemistry, nucleotides in a tRNA, complementary to a carbon and nitrogen sources, such as carbon biochemistry, and physics. The data are often codon for an amino acid in an mRNA. dioxide and ammonia. nucleic acid or protein sequence or structural antigen: A molecule capable of eliciting the auxin: A plant growth hormone. data, but can also involve experimental data synthesis of a specifi c antibody in vertebrates. auxotrophic mutant (auxotroph): A from many sources, patient statistics, and antiparallel: Describes two linear polymers mutant organism defective in the synthesis of materials in the scientifi c literature. Bioinfor- that are opposite in polarity or orientation. a particular biomolecule, which must therefore matics research focuses on methods for data storage, retrieval, and analysis. antiport: Cotransport of two solutes across a be supplied for the organism’s growth. membrane in opposite directions. Avogadro’s number (N): The number of biosphere: All the living matter on or in the earth, the seas, and the atmosphere. apoenzyme: The protein portion of an molecules in a gram molecular weight (a mole) 23 enzyme, exclusive of any organic or inorganic of any compound (6.02 3 10 ). biotin: A vitamin; an enzymatic cofactor cofactors or prosthetic groups that might be involved in carboxylation reactions. B lymphocyte (B cell): One of a class of required for catalytic activity. b apolipoprotein: The protein component of a blood cells (lymphocytes), responsible for the lipoprotein. Bacteria: One of the fi ve kingdoms of living production of circulating antibodies. organisms; bacteria have a plasma membrane apoprotein: The protein portion of a protein, bond energy: The energy required to break but no internal organelles or nucleus. exclusive of any organic or inorganic cofactors a bond. or prosthetic groups that might be required for bacteriophage: A virus capable of replicating branch migration: Movement of the branch activity. in a bacterial cell; also called phage. point in a branched DNA formed from two DNA molecules with identical sequences. See apoptosis: (app9-a-toe9-sis) Programmed baculovirus: Any of a group of double-stranded also Holliday intermediate. cell death in which a cell brings about its own DNA viruses that infect invertebrates, particu- death and lysis, in response to a signal from larly insects, and are widely used for purposes brown adipose tissue (BAT): Thermo- outside or programmed in its genes, by sys- of protein expression in biotechnology. genic adipose tissue rich in mitochondria that tematically degrading its own macromolecules. basal metabolic rate: An animal’s rate of contain the uncoupling protein thermogenin, which uncouples electron transfer through the aptamer: Oligonucleotide that binds specifi - oxygen consumption when at complete rest, respiratory chain from ATP synthesis. Com- cally to one molecular target, usually selected long after a meal. pare white adipose tissue. by an iterative cycle of affi nity-based enrich- base pair: Two nucleotides in nucleic acid ment (SELEX). chains that are paired by hydrogen bonding of buffer: A system capable of resisting changes aquaporin (AQP): A member of a family of their bases; for example, A with T or U, and G in pH, consisting of a conjugate acid-base pair integral membrane proteins that mediate the with C. in which the ratio of proton acceptor to proton fl ow of water across membranes. BAT: See brown adipose tissue. donor is near unity. Archaea: One of the fi ve kingdoms of living B cell: See B lymphocyte. organisms; includes many species that thrive ␤ conformation: An extended, zigzag c in extreme environments of high ionic arrangement of a polypeptide chain; a com- calorie: The amount of heat required to raise strength, high temperature, or low pH. mon secondary structure in proteins. the temperature of 1.0 g of water from 14.5 asymmetric carbon atom: A carbon atom ␤ oxidation: Oxidative degradation of fatty to 15.5 8C. One calorie (cal) equals 4.18 that is covalently bonded to four different acids into acetyl-CoA by successive oxida- joules (J). BMGlossary.indd Page G-3 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-3

Calvin cycle: The cyclic pathway in plants cDNA library: A collection of cloned DNA chromatophore: A compound or moiety that fi xes carbon dioxide and produces triose fragments derived entirely from the comple- (natural or synthetic) that absorbs visible or phosphates. ment of mRNA being expressed in a particular ultraviolet light. CAM plants: Succulent plants of hot, dry cli- organism or cell type under a defi ned set of chromosome: A single large DNA molecule conditions. mates, in which CO2 is fi xed into oxaloacetate and its associated proteins, containing many in the dark, then fi xed by rubisco in the light cellular differentiation: The process in genes; stores and transmits genetic information. when stomata close to exclude O2. which a precursor cell becomes specialized to chylomicron: A plasma lipoprotein consisting cAMP: See cyclic AMP. carry out a particular function, by acquiring a of a large droplet of triacylglycerols stabilized new complement of proteins and RNA. cAMP receptor protein (CRP): In bacteria, by a coat of protein and phospholipid; carries a specifi c regulatory protein that controls initi- central dogma: The organizing principle of lipids from the intestine to the tissues. ation of transcription of the genes that produce molecular biology: genetic information fl ows circular dichroism spectroscopy: A method the enzymes required for the cell to use some from DNA to RNA to protein. used to characterize the degree of folding in a other nutrient when glucose is lacking; also centromere: A specialized site in a chromo- protein, based on differences in the absorption called catabolite gene activator protein (CAP). some, serving as the attachment point for the of right-handed versus left-handed circularly CAP: See cAMP receptor protein. mitotic or meiotic spindle. polarized light. capsid: The protein coat of a virion or virus cerebroside: Sphingolipid containing one cis and trans isomers: See geometric isomers. particle. sugar residue as a head group. cistron: A unit of DNA or RNA corresponding carbanion: A negatively charged carbon channeling: The direct transfer of a reaction to one gene. atom. product (common intermediate) from the ac- citric acid cycle: A cyclic pathway for the tive site of an enzyme to the active site of the carbocation: A positively charged carbon oxidation of acetyl residues to carbon dioxide, enzyme catalyzing the next step in a pathway. atom; also called a carbonium ion. in which formation of citrate is the fi rst step; chaperone: Any of several classes of proteins also known as the Krebs cycle or tricarboxylic carbohydrate: A polyhydroxy aldehyde or protein complexes that catalyze the accu- acid cycle. or ketone, or substance that yields such a rate folding of proteins in all cells. clones: The descendants of a single cell. compound on hydrolysis. Many carbohydrates cloning: The production of large numbers of have the empirical formula (CH2O)n; some also chaperonin: One of two major classes of contain nitrogen, phosphorus, or sulfur. chaperones found in virtually all organisms; a identical DNA molecules, cells, or organisms complex of proteins that functions in protein from a single ancestral DNA molecule, cell, or carbon-assimilation reactions: Reaction folding, either GroES/GroEL in bacteria or organism. sequence in which atmospheric CO is con- 2 Hsp60 in eukaryotes. verted into organic compounds. closed system: A system that exchanges nei- ther matter nor energy with the surroundings. carbon-fi xation reactions: The reactions, chemiosmotic coupling: Coupling of ATP See also system. catalyzed by rubisco during photosynthesis or synthesis to electron transfer via a transmem- brane difference in charge and pH. by other carboxylases, in which atmospheric cobalamin: See coenzyme B12.

CO2 is initially incorporated (fi xed) into an chemiosmotic theory: The theory that en- coding strand: In DNA transcription, the DNA organic compound. ergy derived from electron transfer reactions strand identical in base sequence to the RNA carbonium ion: See carbocation. is temporarily stored as a transmembrane dif- transcribed from it, with U in the RNA in place ference in charge and pH, which subsequently of T in the DNA; as distinct from the template carboxyl-terminal residue: The only amino drives the formation of ATP in oxidative phos- strand. Also called the nontemplate strand. acid residue in a polypeptide chain with a free phorylation and photophosphorylation. ␣-carboxyl group; defi nes the carboxyl termi- codon: A sequence of three adjacent nucleo- nus of the polypeptide. chemotaxis: A cell’s sensing of and movement tides in a nucleic acid that codes for a specifi c toward or away from a specifi c chemical agent. amino acid. cardiolipin: A membrane phospholipid in which two phosphatidic acid moieties share a chemotroph: An organism that obtains coenzyme: An organic cofactor required for single glycerol head group. energy by metabolizing organic compounds the action of certain enzymes; often has a derived from other organisms. vitamin component. carnitine shuttle: Mechanism for moving fatty acids from the cytosol to the mitochon- chiral center: An atom with substituents coenzyme A: A pantothenic acid–containing drial matrix as fatty esters of carnitine. arranged so that the molecule is not superpos- coenzyme that serves as an acyl group carrier able on its mirror image. in certain enzymatic reactions. carotenoids: Lipid-soluble photosynthetic pigments made up of isoprene units. chiral compound: A compound that contains coenzyme B12: An enzymatic cofactor derived an asymmetric center (chiral atom or chiral from the vitamin cobalamin, involved in cer- cascade: See enzyme cascade. center) and thus can occur in two nonsuper- tain types of carbon skeletal rearrangements. catabolism: The phase of intermediary posable mirror-image forms (enantiomers). cofactor: An inorganic ion or a coenzyme metabolism concerned with the energy- chlorophylls: A family of green pigments that required for enzyme activity. yielding degradation of nutrient molecules. function as receptors of light energy in photo- cognate: Describes two biomolecules that catabolite gene activator protein (CAP): synthesis; magnesium-porphyrin complexes. normally interact; for example, an enzyme and See cAMP receptor protein. chloroplast: Chlorophyll-containing photo- its usual substrate, or a receptor and its usual catalytic site: See active site. synthetic organelle in some eukaryotic cells. ligand. catecholamines: Hormones, such as epineph- chondroitin sulfate: One of a family of sul- cohesive ends: See sticky ends. rine, that are amino derivatives of catechol. fated glycosaminoglycans, a major component cointegrate: An intermediate in the migration catenane: Two or more circular polymeric of the extracellular matrix. of certain DNA transposons in which the donor molecules interlinked by one or more nonco- chromatin: A fi lamentous complex of DNA, DNA and target DNA are covalently attached. valent topological links, resembling the links histones, and other proteins, constituting the colligative properties: Properties of a solu- of a chain. eukaryotic chromosome. tion that depend on the number of solute par- cation-exchange resin: An insoluble polymer chromatography: A process in which com- ticles per unit volume; for example, freezing- with fi xed negative charges, used in the chro- plex mixtures of molecules are separated by point depression. matographic separation of cationic substances. many repeated partitionings between a fl owing combinatorial control: Use of combinations cDNA: See complementary DNA. (mobile) phase and a stationary phase. of a limited repertoire of regulatory proteins BMGlossary.indd Page G-4 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-4 Glossary

to provide gene-specifi c regulation of many coupled reactions: Two chemical reactions degenerate code: A code in which a single individual genes. that have a common intermediate and thus a element in one language is specifi ed by more competitive inhibition: A type of enzyme means of energy transfer from one to the other. than one element in a second language. inhibition reversed by increasing the substrate covalent bond: A chemical bond that involves dehydrogenases: Enzymes that catalyze concentration; a competitive inhibitor gener- sharing of electron pairs. the removal of pairs of hydrogen atoms from ally competes with the normal substrate or substrates. C4 plants: Plants (generally tropical) in which ligand for a protein’s binding site. CO2 is fi rst fi xed into a four-carbon compound deletion mutation: A mutation resulting complementary: Having a molecular surface (oxaloacetate or malate) before entering the from the deletion of one or more nucleotides with chemical groups arranged to interact Calvin cycle via rubisco. from a gene or chromosome. specifi cally with chemical groups on another cristae: Infoldings of the inner mitochondrial ⌬G: See free-energy change. molecule. membrane. ⌬G‡: See activation energy. complementary DNA (cDNA): A DNA com- CRP: See cAMP receptor protein. ⌬G9Њ: See standard free-energy change. plementary to a specifi c mRNA, used in DNA cruciform: Secondary structure in double- cloning; usually made by reverse transcriptase. denaturation: Partial or complete unfolding stranded RNA or DNA in which the double of the specifi c native conformation of a poly- condensation: A reaction type in which two helix is denatured at palindromic repeat peptide chain, protein, or nucleic acid such compounds are joined with the elimination of sequences in each strand, and each separated that the function of the molecule is lost. water. strand is paired internally to form opposing denatured protein: A protein that has lost confi guration: The spatial arrangement of an hairpin structures. See also hairpin. enough of its native conformation by exposure organic molecule that is conferred by the pres- cyclic AMP (cAMP, adenosine 39, 59-cyclic to a destabilizing agent such as heat or deter- ence of either (1) double bonds, about which monophosphate): A second messenger; its gent that its function is lost. there is no freedom of rotation, or (2) chiral formation in a cell by adenylyl cyclase is stimu- de novo pathway: Pathway for the synthesis centers, around which substituent groups are lated by certain hormones or other molecular of a biomolecule, such as a nucleotide, from arranged in a specifi c sequence. Confi gura- signals. tional isomers cannot be interconverted with- simple precursors; as distinct from a salvage cyclic electron fl ow: In chloroplasts, the out breaking one or more covalent bonds. pathway. light-induced fl ow of electrons originating deoxyribonucleic acid: See DNA. conformation: A spatial arrangement of from and returning to photosystem I. substituent groups that are free to assume dif- deoxyribonucleotides: Nucleotides contain- cyclic photophosphorylation: ATP syn- ferent positions in space, without breaking any ing 2-deoxy-D-ribose as the pentose component. thesis driven by cyclic electron fl ow through bonds, because of the freedom of bond rotation. photosystem I. desaturases: Enzymes that catalyze the in- conjugate acid-base pair: A proton donor troduction of double bonds into the hydrocar- cyclin: One of a family of proteins that and its corresponding deprotonated species; bon portion of fatty acids. activate cyclin-dependent protein kinases and for example, acetic acid (donor) and acetate thereby regulate the cell cycle. desensitization: Universal process by which (acceptor). sensory mechanisms cease to respond after cytochrome P-450: A family of heme- conjugated protein: A protein containing prolonged exposure to the specifi c stimulus containing enzymes, with a characteristic one or more prosthetic groups. they detect. absorption band at 450 nm, that participate in conjugate redox pair: An electron donor desolvation: In aqueous solution, the release biological hydroxylations with O2. and its corresponding electron acceptor form; of bound water surrounding a solute. ϩ 2ϩ cytochromes: Heme proteins serving as elec- for example, Cu (donor) and Cu (accep- diabetes mellitus: A group of metabolic tor), or NADH (donor) and NADϩ (acceptor). tron carriers in respiration, photosynthesis, and other oxidation-reduction reactions. diseases with symptoms that result from a consensus sequence: A DNA or amino acid defi ciency in insulin production or utilization; cytokine: One of a family of small secreted sequence consisting of the residues that most characterized by a failure in glucose transport proteins (such as interleukins or interferons) commonly occur at each position in a set of from the blood into cells at normal glucose that activate cell division or differentiation similar sequences. concentrations. by binding to plasma membrane receptors in conservative substitution: Replacement target cells. dialysis: Removal of small molecules from a of an amino acid residue in a polypeptide by solution of a macromolecule by their diffusion cytokinesis: The fi nal separation of daughter another residue with similar properties; for through a semipermeable membrane into a cells following mitosis. example, substitution of Glu by Asp. suitably buffered solution. cytoplasm: The portion of a cell’s contents constitutive enzymes: Enzymes required differential centrifugation: Separation of outside the nucleus but within the plasma mem- at all times by a cell and present at some con- cell organelles or other particles of different brane; includes organelles such as mitochondria. stant level; for example, many enzymes of the size by their different rates of sedimentation in central metabolic pathways. Sometimes called cytoskeleton: The fi lamentous network that a centrifugal fi eld. housekeeping enzymes. provides structure and organization to the differentiation: Specialization of cell structure cytoplasm; includes actin fi laments, microtu- contig: A series of overlapping clones or a and function during growth and development. continuous sequence defi ning an uninter- bules, and intermediate fi laments. diffusion: The net movement of molecules in rupted section of a chromosome. cytosol: The continuous aqueous phase of the the direction of lower concentration. contour length: The length of a helical poly- cytoplasm, with its dissolved solutes; excludes meric molecule as measured along its helical the organelles such as mitochondria. digestion: Enzymatic hydrolysis of major axis. nutrients in the gastrointestinal system to yield their simpler components. cooperativity: The characteristic of an en- d zyme or other protein in which binding of the dalton: Unit of atomic or molecular weight; diploid: Having two sets of genetic information; fi rst molecule of a ligand changes the affi nity for 1 dalton (Da) is the weight of a hydrogen describes a cell with two chromosomes of each 224 the second molecule. In positive cooperativity, atom (1.66 3 10 g). type. Compare haploid. the affi nity for the second ligand molecule in- dark reactions: See carbon-assimilation disaccharide: A carbohydrate consisting of creases; in negative cooperativity, it decreases. reactions. two covalently joined monosaccharide units. cotransport: The simultaneous transport, by deamination: The enzymatic removal of dissociation constant: An equilibrium con-

a single transporter, of two solutes across a amino groups from biomolecules such as stant (Kd) for the dissociation of a complex of membrane. See also antiport; symport. amino acids or nucleotides. two or more biomolecules into its components; BMGlossary.indd Page G-5 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-5

for example, dissociation of a substrate from electron donor: A substance that donates enzyme activates another (often by phosphor- an enzyme. electrons in an oxidation-reduction reaction. ylation), which activates a third, and so on. disulfi de bond: A covalent bond involving the electron transfer: Movement of electrons The effect of a catalyst activating a catalyst is oxidative linkage of two Cys residues, from the from electron donor to electron acceptor; a large amplifi cation of the signal that initiated same or different polypeptide chains, forming especially, from substrates to oxygen via the the cascade. a cystine residue. carriers of the respiratory (electron-transfer) epigenetic: Describes any inherited charac- DNA (deoxyribonucleic acid): A polynu- chain. teristic of a living organism that is acquired cleotide with a specifi c sequence of deoxyri- electrophile: An electron-defi cient group by means that do not involve the nucleotide bonucleotide units covalently joined through with a strong tendency to accept electrons sequence of the parental chromosomes; for 39,59-phosphodiester bonds; serves as the from an electron-rich group (nucleophile). example, covalent modifi cations of histones. carrier of genetic information. electrophoresis: Movement of charged epimerases: Enzymes that catalyze the DNA chimera: DNA containing genetic infor- solutes in response to an electrical fi eld; often reversible interconversion of two epimers. mation derived from two different species. used to separate mixtures of ions, proteins, or epimers: Two stereoisomers differing in DNA chip: Informal term for a DNA microarray, nucleic acids. confi guration at one asymmetric center in a referring to the small size of typical microarrays. elongation factors: (1) Proteins that func- compound having two or more asymmetric DNA cloning: See cloning. tion in the elongation phase of eukaryotic centers. DNA library: A collection of cloned DNA transcription. (2) Specifi c proteins required epithelial cell: Any cell that forms part of the fragments. in the elongation of polypeptide chains by outer covering of an organism or organ. ribosomes. DNA ligases: Enzymes that creates a phos- epitope: An antigenic determinant; the par- phodiester bond between the 39 end of one eluate: The effl uent from a chromatographic ticular chemical group or groups in a macromol- DNA segment and the 59 end of another. column. ecule (antigen) to which a given antibody binds. DNA looping: The interaction of proteins enantiomers: Stereoisomers that are non- epitope tag: A protein sequence or domain bound at distant sites on a DNA molecule so superposable mirror images of each other. bound by some well-characterized antibody. that the intervening DNA forms a loop. endergonic reaction: A chemical reaction equilibrium: The state of a system in which DNA microarray: A collection of DNA that consumes energy (that is, for which DG is no further net change is occurring; the free sequences immobilized on a solid surface, with positive). energy is at a minimum.

individual sequences laid out in patterned endocrine: Pertaining to cellular secretions equilibrium constant (Keq): A constant, arrays that can be probed by hybridization. that enter the bloodstream and have their characteristic for each chemical reaction, that DNA polymerase: An enzyme that catalyzes effects on distant tissues. relates the specifi c concentrations of all reac- template-dependent synthesis of DNA from its endocytosis: The uptake of extracellular tants and products at equilibrium at a given deoxyribonucleoside 59-triphosphate precursors. material by its inclusion in a vesicle temperature and pressure. DNA supercoiling: The coiling of DNA upon (endosome) formed by invagination of the erythrocyte: A cell containing large amounts itself, generally as a result of bending, under- plasma membrane. of hemoglobin and specialized for oxygen winding, or overwinding of the DNA helix. endonucleases: Enzymes that hydrolyze the transport; a red blood cell. DNA transposition: See transposition. interior phosphodiester bonds of a nucleic essential amino acids: Amino acids that can- acid—that is, act at bonds other than the domain: A distinct structural unit of a poly- not be synthesized by humans (and other verte- terminal bonds. peptide; domains may have separate functions brates) and must be obtained from the diet. and may fold as independent, compact units. endoplasmic reticulum: An extensive sys- essential fatty acids: The group of polyun- tem of double membranes in the cytoplasm of double helix: The natural coiled conforma- saturated fatty acids produced by plants, but eukaryotic cells; it encloses secretory channels tion of two complementary, antiparallel DNA not by humans; required in the human diet. and is often studded with ribosomes (rough chains. ethanol fermentation: The anaerobic endoplasmic reticulum). double-reciprocal plot: A plot of 1/V versus conversion of glucose to ethanol via glycoly- 0 endothermic reaction: A chemical reaction 1/[S], which allows a more accurate determina- sis; also called alcohol fermentation. See also that takes up heat (that is, for which DH is tion of V and K than a plot of V versus [S]; fermentation. max m 0 positive). also called the Lineweaver-Burk plot. euchromatin: The regions of interphase end-product inhibition: See feedback chromosomes that stain diffusely, as opposed e inhibition. to the more condensed, heavily staining, E98: See standard reduction potential. enhancers: DNA sequences that facilitate the heterochromatin. These are often regions in ECM: See extracellular matrix. expression of a given gene; may be located which genes are being actively expressed. electrochemical gradient: The resultant of a few hundred, or even thousand, base pairs eukaryote: A unicellular or multicellular the gradients of concentration and of electric away from the gene. organism with cells having a membrane- charge of an ion across a membrane; the driv- enthalpy (H): The heat content of a system. bounded nucleus, multiple chromosomes, ing force for oxidative phosphorylation and enthalpy change (DH): For a reaction, and internal organelles. photophosphorylation. approximately equal to the difference between excited state: An energy-rich state of an electrochemical potential: The energy the energy used to break bonds and the atom or molecule, produced by the absorption required to maintain a separation of charge energy gained by the formation of new ones. of light energy; as distinct from ground state. and of concentration across a membrane. entropy (S): The extent of randomness or exergonic reaction: A chemical reaction that electrogenic: Contributing to an electrical disorder in a system. proceeds with the release of free energy (that potential across a membrane. enzyme: A biomolecule, either protein or is, for which DG is negative). electron acceptor: A substance that receives RNA, that catalyzes a specifi c chemical reac- exocytosis: The fusion of an intracellular electrons in an oxidation-reduction reaction. tion. It does not affect the equilibrium of the vesicle with the plasma membrane, releasing electron carrier: A protein, such as a fl a- catalyzed reaction; it enhances the rate of the the vesicle contents to the extracellular space. voprotein or a cytochrome, that can revers- reaction by providing a reaction path with a exon: The segment of a eukaryotic gene that ibly gain and lose electrons; functions in the lower activation energy. encodes a portion of the fi nal product of the transfer of electrons from organic nutrients to enzyme cascade: A series of reactions, often gene; a segment of RNA that remains after oxygen or some other terminal acceptor. involved in regulatory events, in which one posttranscriptional processing and is BMGlossary.indd Page G-6 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-6 Glossary

transcribed into a protein or incorporated into fl avin-linked dehydrogenases: Dehydroge- transfer of energy between reporter chromo- the structure of an RNA. See also intron. nases requiring one of the ribofl avin coen- phores when one is excited and the fl uores- exonucleases: Enzymes that hydrolyze only zymes, FMN or FAD. cence emitted from the other is quantifi ed. those phosphodiester bonds that are in the fl avin nucleotides: Nucleotide coenzymes functional group: The specifi c atom or group terminal positions of a nucleic acid. (FMN and FAD) containing ribofl avin. of atoms that confers a particular chemical exothermic reaction: A chemical reaction fl avoprotein: An enzyme containing a fl avin property on a biomolecule. that releases heat (that is, for which DH is nucleotide as a tightly bound prosthetic group. fusion protein: (1) One of a family of pro- negative). fl ippases: Membrane proteins in the ABC teins that facilitate membrane fusion. (2) The expression vector: See vector. transporter family that catalyze the movement protein product of a gene created by the fusion of two distinct genes or portions of genes. extracellular matrix (ECM): An inter- of phospholipids from the extracellular leafl et woven combination of glycosaminoglycans, to the cytosolic leafl et of a membrane bilayer. futile cycle: A cycle of enzyme-catalyzed proteoglycans, and proteins, just outside the fl oppases: Membrane proteins in the ABC reactions that results in release of thermal plasma membrane, that provides cell anchor- transporter family that catalyze movement of energy by the hydrolysis of ATP. age, positional recognition, and traction during phospholipids from the cytosolic leafl et to the cell migration. extracellular leafl et of a membrane bilayer. g extrahepatic: Describes all tissues outside fl uid mosaic model: A model describing bio- Gi: See inhibitory G protein. the liver; implies the centrality of the liver in logical membranes as a fl uid lipid bilayer with Gs: See stimulatory G protein. metabolism. embedded proteins; the bilayer exhibits both gametes: Reproductive cells with a haploid structural and functional asymmetry. gene content; sperm or egg cells. fl uorescence: Emission of light by excited ganglioside: Sphingolipid containing a f molecules as they revert to the ground state. complex oligosaccharide as a head group; facilitated diffusion: See passive transport. fl uorescence recovery after photobleach- especially common in nervous tissue. FAD (fl avin adenine dinucleotide): ing: See FRAP. GEFs: See guanosine nucleotide–exchange The coenzyme of some oxidation-reduction fl uorescence resonance energy transfer: factors. enzymes; contains ribofl avin. See FRET. gel fi ltration: See size-exclusion F1 ATPase: The multiprotein subunit of FMN (fl avin mononucleotide): Ribofl avin chromatography. ATP synthase that has the ATP-synthesizing phosphate, a coenzyme of certain oxidation- gene: A chromosomal segment that codes for catalytic sites. It interacts with the Fo subunit reduction enzymes. a single functional polypeptide chain or RNA of ATP synthase, coupling proton movement fold: See motif. molecule. to ATP synthesis. footprinting: A technique for identifying the gene expression: Transcription, and in the fatty acid: A long-chain aliphatic carboxylic nucleic acid sequence bound by a DNA- or case of proteins, translation, to yield the prod- acid found in natural fats and oils; also a compo- RNA-binding protein. uct of a gene; a gene is expressed when its nent of membrane phospholipids and glycolipids. biological product is present and active. fraction: A portion of a biological sample that feedback inhibition: Inhibition of an allo- has been subjected to a procedure designed to gene fusion: The enzymatic attachment of steric enzyme at the beginning of a metabolic separate macromolecules based on a property one gene, or part of a gene, to another. sequence by the end product of the sequence; such as solubility, net charge, molecular general acid-base catalysis: Catalysis also known as end-product inhibition. weight, or function. involving proton transfer(s) to or from a fermentation: Energy-yielding anaerobic fractionation: The process of separating the molecule other than water. breakdown of a nutrient molecule, such as proteins or other components of a complex genetic code: The set of triplet code words glucose, without net oxidation; yields lactate, molecular mixture into fractions based on in DNA (or mRNA) coding for the amino acids ethanol, or some other simple product. differences in properties such as solubility, net of proteins. fi brin: A protein factor that forms the cross- charge, molecular weight, or function. genetic engineering: Any process by which linked fi bers in blood clots. frame shift: A mutation caused by insertion genetic material, particularly DNA, is altered fi brinogen: The inactive precursor protein of or deletion of one or more paired nucleotides, by a molecular biologist. fi brin. changing the reading frame of codons during genetic map: A diagram showing the relative fi broblast: A cell of the connective tissue that protein synthesis; the polypeptide product has sequence and position of specifi c genes along secretes connective tissue proteins such as a garbled amino acid sequence beginning at a chromosome. collagen. the mutated codon. genome: All the genetic information encoded fi brous proteins: Insoluble proteins that FRAP (fl uorescence recovery after photo- in a cell or virus. serve a protective or structural role; contain bleaching): A technique used to quantify the genomic library: A DNA library containing polypeptide chains that generally share a com- diffusion of membrane components (lipids or DNA segments that represent all (or most) of mon secondary structure. proteins) in the plane of the bilayer. the sequences in an organism’s genome. fi rst law of thermodynamics: The law stat- free energy (G): The component of the genomics: A science devoted broadly to ing that, in all processes, the total energy of total energy of a system that can do work at the understanding of cellular and organism the universe remains constant. constant temperature and pressure. genomes. Fischer projection formulas: A method free energy of activation (DG‡): See genotype: The genetic constitution of an for representing molecules that shows the activation energy. organism, as distinct from its physical charac- confi guration of groups around chiral centers; free-energy change (DG): The amount teristics, or phenotype. also known as projection formulas. of free energy released (negative DG) or geometric isomers: Isomers related by rota- 59 end: The end of a nucleic acid that lacks absorbed (positive DG) in a reaction at tion about a double bond; also called cis and a nucleotide bound at the 59 position of the constant temperature and pressure. trans isomers. terminal residue. free radical: See radical. germ-line cell: A type of animal cell that is fl agellum: A cell appendage used in propul- FRET (fl uorescence resonance energy formed early in embryogenesis and may multi- sion. Bacterial fl agella have a much simpler transfer): A technique for estimating the ply by mitosis or produce by meiosis cells that structure than eukaryotic fl agella, which are distance between two proteins or two domains develop into gametes (egg or sperm cells). similar to cilia. of a protein by measuring the nonradiative GFP: See green fl uorescent protein. BMGlossary.indd Page G-7 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-7

globular proteins: Soluble proteins with a Golgi complex: A complex membranous or- to form an antiparallel duplex helix that is globular (somewhat rounded) shape. ganelle of eukaryotic cells; functions in the post- closed at one end. glucogenic: Capable of being converted into translational modifi cation of proteins and their half-life: The time required for the disappear- glucose or glycogen by the process of secretion from the cell or incorporation into the ance or decay of one-half of a given component gluconeogenesis. plasma membrane or organellar membranes. in a system. gluconeogenesis: The biosynthesis of a GPCRs: See G protein–coupled receptors. haploid: Having a single set of genetic infor- carbohydrate from simpler, noncarbohydrate GPI-anchored protein: A protein held to mation; describes a cell with one chromosome precursors such as oxaloacetate or pyruvate. the outer monolayer of the plasma membrane of each type. Compare diploid. GLUT: Designation for a family of membrane by its covalent attachment through a short haplotype: A combination of alleles of differ- proteins that transport glucose. oligosaccharide chain to a phosphatidylinositol ent genes located suffi ciently close together on glycan: A polymer of monosaccharide units molecule in the membrane. a chromosome that they tend to be inherited joined by glycosidic bonds; polysaccharide. G protein–coupled receptor kinases together. glyceroneogenesis: The synthesis in adipo- (GRKs): A family of protein kinases that hapten: A small molecule that, when linked to cytes of glycerol 3-phosphate from pyruvate phosphorylate Ser and Thr residues near the a larger molecule, elicits an immune response. carboxyl terminus of G protein–coupled recep- for use in triacylglycerol synthesis. Haworth perspective formulas: A method tors, initiating their internalization. glycerophospholipid: An amphipathic lipid for representing cyclic chemical structures so with a glycerol backbone; fatty acids are ester- G protein–coupled receptors (GPCRs): as to defi ne the confi guration of each substituent linked to C-1 and C-2 of glycerol, and a polar A large family of membrane receptor proteins group; commonly used for representing sugars. with seven transmembrane helical segments, alcohol is attached through a phosphodiester helicases: Enzymes that catalyze the separa- often associating with G proteins to transduce linkage to C-3. tion of strands in a DNA molecule before an extracellular signal into a change in cellular glycoconjugate: A compound containing a replication. metabolism; also called heptahelical receptors. carbohydrate component bound covalently to heme: The iron-porphyrin prosthetic group of G proteins: A large family of GTP-binding a protein or lipid, forming a glycoprotein or heme proteins. glycolipid. proteins that act in intracellular signaling heme protein: A protein containing a heme glycogenesis: The process of converting pathways and in membrane traffi cking. Active as a prosthetic group. glucose to glycogen. when GTP is bound, they self-inactivate by converting GTP to GDP. Also called guanosine hemoglobin: A heme protein in erythrocytes; glycogenin: The protein that both primes the nucleotide–binding proteins. functions in oxygen transport. synthesis of new glycogen chains and catalyzes the polymerization of the fi rst few sugar resi- gram molecular weight: For a compound, Henderson-Hasselbalch equation: An dues of each chain before glycogen synthase the weight in grams that is numerically equal to equation relating the pH, the pKa, and the ratio 2 continues the extension. its molecular weight; the weight of one mole. of the concentrations of proton-acceptor (A ) and proton-donor (HA) species in a solution: glycogenolysis: The enzymatic breakdown of grana: Stacks of thylakoids, fl attened mem- 2 stored (not dietary) glycogen. branous sacs or disks, in chloroplasts. [A ] pH 5 p⌲a 1 log . glycolate pathway: The metabolic pathway green fl uorescent protein (GFP): A small [HA] protein from a marine organism that produces in photosynthetic organisms that converts heparan sulfate: A sulfated polymer of alter- a bright fl uorescence in the green region of the glycolate produced during photorespiration nating N-acetylglucosamine and a uronic acid, visible spectrum. Fusion proteins with GFP are into 3-phosphoglycerate. either glucuronic or iduronic acid; typically commonly used to determine the subcellular glycolipid: A lipid containing a carbohydrate found in the extracellular matrix. location of the fused protein by fl uorescence group. microscopy. hepatocyte: The major cell type of liver tissue. glycolysis: The catabolic pathway by which a ground state: The normal, stable form of an heptahelical receptors: See G protein– molecule of glucose is broken down into two coupled receptors. molecules of pyruvate. atom or molecule; as distinct from the excited state. heteropolysaccharide: A polysaccharide glycome: The full complement of carbohy- containing more than one type of sugar. drates and carbohydrate-containing molecules group transfer potential: A measure of the heterotroph: An organism that requires of a cell or tissue under a particular set of ability of a compound to donate an activated complex nutrient molecules, such as glucose, conditions. group (such as a phosphate or acyl group); generally expressed as the standard free as a source of energy and carbon. glycomics: The systematic characterization of energy of hydrolysis. the glycome. heterotropic: Describes an allosteric modula- growth factors: Proteins or other molecules tor that is distinct from the normal ligand. glycoprotein: A protein containing a carbohy- that act from outside a cell to stimulate cell drate group. heterotropic enzyme: An allosteric enzyme growth and division. requiring a modulator other than its substrate. glycosaminoglycan: A heteropolysaccharide GTPase activator proteins (GAPs): Regu- of two alternating units: one is either hexose: A simple sugar with a backbone latory proteins that bind activated G proteins N-acetylglucosamine or N-acetylgalactosamine; containing six carbon atoms. and stimulate their intrinsic GTPase activity, the other is a uronic acid (usually glucuronic hexose monophosphate pathway: See speeding their self-inactivation. acid). Formerly called a mucopolysaccharide. pentose phosphate pathway. guanosine nucleotide–binding proteins: glycosidic bonds: See O-glyosidic bonds. high-performance liquid chromatography See G proteins. glycosphingolipid: An amphipathic lipid with (HPLC): Chromatographic procedure, often guanosine nucleotide–exchange factors a sphingosine backbone to which are attached conducted at relatively high pressures using (GEFs): Regulatory proteins that bind to a long-chain fatty acid and a polar alcohol. automated equipment, which permits refi ned and activate G proteins by stimulating the glyoxylate cycle: A variant of the citric acid and highly reproducible profi les. exchange of bound GDP for GTP. cycle, for the net conversion of acetate into Hill coeffi cient: A measure of cooperative succinate and, eventually, new carbohydrate; interaction between protein subunits. present in bacteria and some plant cells. h Hill reaction: The evolution of oxygen and glyoxysome: A specialized peroxisome con- hairpin: Secondary structure in single-stranded photoreduction of an artifi cial electron accep- taining the enzymes of the glyoxylate cycle; RNA or DNA, in which complementary parts of tor by a chloroplast preparation in the absence found in cells of germinating seeds. a palindromic repeat fold back and are paired of carbon dioxide. BMGlossary.indd Page G-8 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-8 Glossary

histones: The family of basic proteins that as oxygen or nitrogen) and a hydrogen atom inhibits a neighboring membrane enzyme such associate tightly with DNA in the chromo- covalently linked to a second electronegative as adenylyl cyclase. Compare stimulatory G

somes of all eukaryotic cells. atom. protein (Gs). Holliday intermediate: An intermediate in hydrolases: Enzymes (proteases, lipases, initiation codon: AUG (sometimes GUG genetic recombination in which two double- phosphatases, nucleases, for example) that or, even more rarely, UUG in bacteria and stranded DNA molecules are joined by a catalyze hydrolysis reactions. archaea); codes for the fi rst amino acid in a reciprocal crossover involving one strand of hydrolysis: Cleavage of a bond, such as an polypeptide sequence: N-formylmethionine in each molecule. anhydride or peptide bond, by the addition of bacteria; methionine in archaea and eukaryotes. holoenzyme: A catalytically active enzyme, the elements of water, yielding two or more initiation complex: A complex of a ribosome including all necessary subunits, prosthetic products. with an mRNA and the initiating Met-tRNAMet groups, and cofactors. hydronium ion: The hydrated hydrogen ion or fMet-tRNAfMet, ready for the elongation 1 homeobox: A conserved DNA sequence of (H3O ). steps. 180 base pairs that encodes a protein domain hydropathy index: A scale that expresses inorganic pyrophosphatase: An enzyme found in many proteins that play a regulatory the relative hydrophobic and hydrophilic that hydrolyzes a molecule of inorganic pyro- role in development. tendencies of a chemical group. phosphate to yield two molecules of (ortho) homeodomain: The protein domain encoded hydrophilic: Polar or charged; describes mol- phosphate; also known as pyrophosphatase. by the homeobox; a regulatory unit that deter- ecules or groups that associate with (dissolve insertion mutation: A mutation caused mines the segmentation of a body plan. easily in) water. by insertion of one or more extra bases, or a homeostasis: The maintenance of a dynamic hydrophobic: Nonpolar; describes molecules mutagen, between successive bases in DNA. steady state by regulatory mechanisms that or groups that are insoluble in water. insertion sequence: Specifi c base sequences compensate for changes in external hydrophobic interactions: The association at either end of a transposable segment of circumstances. of nonpolar groups or compounds with each DNA. homeotic genes: Genes that regulate other in aqueous systems, driven by the ten- in situ: “In position”; that is, in its natural development of the pattern of segments in the dency of the surrounding water molecules to position or location. Drosophila body plan; similar genes are found seek their most stable (disordered) state. integral proteins: Proteins fi rmly bound to in most vertebrates. hyperchromic effect: The large increase a membrane by hydrophobic interactions; as homologs: Genes or proteins that possess a in light absorption at 260 nm occurring as a distinct from peripheral proteins. clear sequence and functional relationship to double-helical DNA unwinds (melts). each other. integrin: One of a large family of heterodi- hypoxia: The metabolic condition in which meric transmembrane proteins that mediate homologous genetic recombination: the supply of oxygen is severely limited. adhesion of cells to other cells or to the extra- Recombination between two DNA molecules of cellular matrix. similar sequence, occurring in all cells; occurs i during meiosis and mitosis in eukaryotes. intercalation: Insertion between stacked immune response: The capacity of a verte- aromatic or planar rings; for example, the homologous proteins: Proteins having brate to generate antibodies to an antigen, a insertion of a planar molecule between two similar sequences and functions in different macromolecule foreign to the organism. successive bases in a nucleic acid. species; for example, the hemoglobins. immunoblotting: A technique that employs intermediary metabolism: In cells, the homotropic: Describes an allosteric modula- antibodies to detect the presence of a protein enzyme-catalyzed reactions that extract chem- tor that is identical to the normal ligand. in a biological sample after the proteins in the ical energy from nutrient molecules and use it homotropic enzyme: An allosteric enzyme sample have been separated by gel electropho- to synthesize and assemble cell components. that uses its substrate as a modulator. resis, transferred to a membrane and immobi- intrinsically disordered proteins: Proteins, lized; also called Western blotting. hormone: A chemical substance synthesized or segments of proteins, that lack a defi nable in small amounts by an endocrine tissue and immunoglobulin: An antibody protein gener- three-dimensional structure in solution. carried in the blood to another tissue, where it ated against, and capable of binding specifi - intron: A sequence of nucleotides in a gene acts as a messenger to regulate the function of cally to, an antigen. the target tissue or organ. that is transcribed but excised before the gene induced fi t: A change in the conformation of is translated; also called intervening sequence. hormone receptor: A protein in, or on the an enzyme in response to substrate binding See also exon. surface of, target cells that binds a specifi c that renders the enzyme catalytically active; in vitro: “In glass”; that is, in the test tube. hormone and initiates the cellular response. also used to denote changes in the conforma- hormone response element (HRE): A short tion of any macromolecule in response to in vivo: “In life”; that is, in the living cell or (12 to 20 bp) DNA sequence that binds recep- ligand binding such that the binding site of the organism. tors for steroid, retinoid, thyroid, and vitamin D macromolecule better conforms to the shape ion channel: An integral protein that provides hormones, altering the expression of the con- of the ligand. for the regulated transport of a specifi c ion, or tiguous genes. Each hormone has a consensus inducer: A signal molecule that, when bound ions, across a membrane. sequence preferred by the cognate receptor. to a regulatory protein, produces an increase ion-exchange chromatography: A process HPLC: See high-performance liquid in the expression of a given gene. for separating complex mixtures of ionic chromatography. induction: An increase in the expression of a compounds by many repeated partitionings HRE: See hormone response element. gene in response to a change in the activity of between a fl owing (mobile) phase and a sta- hyaluronan: A high molecular weight, acidic a regulatory protein. tionary phase consisting of a polymeric resin polysaccharide typically composed of the al- informational macromolecules: Biomol- that contains fi xed charged groups. ternating disaccharide GlcUA(␤1n3)GlcNAc; ecules containing information in the form of ionizing radiation: A type of radiation, such a major component of the extracellular matrix, specifi c sequences of different monomers; for as x rays, that causes loss of electrons from forming larger complexes (proteoglycans) example, many proteins, lipids, polysaccha- some organic molecules, thus making them with proteins and other acidic polysaccha- rides, and nucleic acids. more reactive. rides. Also called hyaluronic acid. inhibitory G protein (Gi): A trimeric ionophore: A compound that binds one or hydrogen bond: A weak electrostatic attrac- GTP-binding protein that, when activated by more metal ions and is capable of diffusing tion between one electronegative atom (such an associated plasma membrane receptor, across a membrane, carrying the bound ion. BMGlossary.indd Page G-9 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-9

ion product of water (KW): The product leader: A short sequence near the amino termi- lipoprotein: A lipid-protein aggregate that of the concentrations of Hϩ and OHϪ in pure nus of a protein or the 59 end of an RNA that has serves to carry water-insoluble lipids in the 1 2 214 water: Kw 5 [H ][OH ] 5 1 3 10 at 25 8C. a specialized targeting or regulatory function. blood. The protein component alone is an iron-sulfur protein: One of a large family of leading strand: The DNA strand that, during apolipoprotein. electron-transfer proteins in which the elec- replication, is synthesized in the same direc- liposome: A small, spherical vesicle composed tron carrier is one or more iron ions associated tion as the replication fork moves. of a phospholipid bilayer, forming spontane- with two or more sulfur atoms of Cys residues leaky mutant: A mutant gene that gives rise ously when phospholipids are suspended in an or of inorganic sulfi de. to a product with a detectable level of biologi- aqueous buffer. isoelectric focusing: An electrophoretic cal activity. lyases: Enzymes that catalyze the removal method for separating macromolecules on the leaving group: The departing or displaced of a group from a molecule to form a double basis of isoelectric pH. molecular group in a unimolecular elimination bond, or the addition of a group to a double isoelectric pH (isoelectric point, pI): The or bimolecular substitution reaction. bond. pH at which a solute has no net electric charge lectin: A protein that binds a carbohydrate, lymphocytes: A subclass of leukocytes and thus does not move in an electric fi eld. commonly an oligosaccharide, with very high involved in the immune response. See also B isoenzymes: See isozymes. affi nity and specifi city, mediating cell-cell lymphocytes; T lymphocytes. isomerases: Enzymes that catalyze the trans- interactions. lysis: Destruction of a plasma membrane or formation of compounds into their positional lethal mutation: A mutation that inactivates (in bacteria) cell wall, releasing the cellular isomers. a biological function essential to the life of the contents and killing the cell. isomers: Any two molecules with the same cell or organism. lysosome: A membrane-bounded organelle of molecular formula but a different arrangement leucine zipper: A protein structural motif in- eukaryotic cells; it contains many hydrolytic of molecular groups. volved in protein-protein interactions in many enzymes and serves as a degrading and recy- isoprene: The hydrocarbon 2-methyl- eukaryotic regulatory proteins; consists of two cling center for unneeded components. 1,3-butadiene, a recurring structural unit interacting ␣ helices in which Leu residues in of terpenoids. every seventh position are a prominent feature m isoprenoid: Any of a large number of natural of the interacting surfaces. macromolecule: A molecule having a molecu- products synthesized by enzymatic poly- leukocyte: White blood cell; involved in the lar weight in the range of a few thousand to merization of two or more isoprene units; also immune response in mammals. many millions. called terpenoid. leukotriene: Any of a class of signaling lipids mass-action ratio (Q): For the reaction isozymes: Multiple forms of an enzyme that derived from arachidonate in the noncyclic aA 1 bB Δ cC 1 dD, the ratio [C]c[D]d/ catalyze the same reaction but differ in amino pathway; modulate smooth muscle activity. [A]a[B]b. acid sequence, substrate affi nity, Vmax, and/or ligand: A small molecule that binds specifi - matrix: The space enclosed by the inner regulatory properties; also called isoenzymes. cally to a larger one; for example, a hormone is membrane of the mitochondrion. the ligand for its specifi c protein receptor. mechanistic target of rapamycin complex k ligases: Enzymes that catalyze condensation 1: See mTORC1. ketogenic: Yielding acetyl-CoA, a precursor reactions in which two atoms are joined using meiosis: A type of cell division in which dip- for ketone body formation, as a breakdown the energy of ATP or another energy-rich loid cells give rise to haploid cells destined to product. compound. become gametes or spores. ketone bodies: Acetoacetate, D-␤-hydroxy- light-dependent reactions: The reactions membrane potential (V ): The difference in butyrate, and acetone; water-soluble fuels m of photosynthesis that require light and can- electrical potential across a biological mem- normally exported by the liver but overpro- not occur in the dark; also known as light brane, commonly measured by the insertion of duced during fasting or in untreated diabetes reactions. a microelectrode. Typical membrane potentials mellitus. Lineweaver-Burk equation: An algebraic vary from 225 mV (by convention, the negative ketose: A simple monosaccharide in which transform of the Michaelis-Menten equation, sign indicates that the inside is negative relative the carbonyl group is a ketone. allowing determination of Vmax and Km by to the outside) to greater than 2100 mV across ketosis: A condition in which the concentra- extrapolation of [S] to infi nity: some plant vacuolar membranes. tion of ketone bodies in the blood, tissues, and 1 Km 1 membrane transport: Movement of a polar urine is abnormally high. 5 1 . solute across a membrane via a specifi c mem- V0 Vmax[S] Vmax kinases: Enzymes that catalyze the phosphor- brane protein (a transporter). linking number: The number of times one ylation of certain molecules by ATP. messenger RNA (mRNA): A class of RNA closed circular DNA strand is wound about kinetics: The study of reaction rates. molecules, each of which is complementary to another; the number of topological links hold- Krebs cycle: See citric acid cycle. one strand of DNA; carries the genetic mes- ing the circles together. K (K ): A kinetic parameter for a mem- sage from the chromosome to the ribosomes. t transport lipases: Enzymes that catalyze the hydrolysis brane transporter analogous to the Michaelis metabolic control: The mechanisms by of triacylglycerols. constant, Km, for an enzymatic reaction. The which the fl ux through a metabolic path- rate of substrate uptake is half-maximal when lipid: A small water-insoluble biomolecule way is changed to refl ect a cell’s altered generally containing fatty acids, sterols, or the substrate concentration equals the Kt. circumstances. isoprenoid compounds. metabolic regulation: The mechanisms by l lipidome: The full complement of lipid- which a cell resists changes in the concen- lagging strand: The DNA strand that, during containing molecules in a cell, organ, or tissue tration of individual metabolites that would replication, must be synthesized in the direc- under a particular set of conditions. otherwise occur when metabolic control tion opposite to that in which the replication lipidomics: The systematic characterization mechanisms alter the fl ux through a pathway. fork moves. of the lipidome. metabolic syndrome: A combination of law of mass action: The law stating that the lipoate (lipoic acid): A vitamin for some medical conditions that together predispose rate of any given chemical reaction is pro- microorganisms; an intermediate carrier of to cardiovascular disease and type 2 diabetes. portional to the product of the activities (or hydrogen atoms and acyl groups in ␣-keto acid They include high blood pressure, high con- concentrations) of the reactants. dehydrogenases. centrations of LDL and triacylglycerol in the BMGlossary.indd Page G-10 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-10 Glossary

blood, slightly elevated fasting blood glucose substrate—are oxidized. One oxygen atom myofi bril: A unit of thick and thin fi laments of concentration, and obesity. is incorporated into the product, the other muscle fi bers. metabolism: The entire set of enzyme- is reduced to H2O. These enzymes often use myosin: A contractile protein; the major com- catalyzed transformations of organic molecules cytochrome P-450 to carry electrons from ponent of the thick fi laments of muscle and in living cells; the sum of anabolism and NADPH to O2. other actin-myosin systems. catabolism. mixed inhibition: The reversible inhibition metabolite: A chemical intermediate in the pattern resulting when an inhibitor molecule n enzyme-catalyzed reactions of metabolism. can bind to either the free enzyme or the NAD, NADP (nicotinamide adenine dinu- metabolome: The complete set of small- enzyme-substrate complex (not necessarily cleotide, nicotinamide adenine dinucleo- molecule metabolites (metabolic inter- with the same affi nity). tide phosphate): Nicotinamide-containing mediates, signals, secondary metabolites) modulator: A metabolite that, when bound coenzymes functioning as carriers of hydrogen present in a given cell or tissue under specifi c to the allosteric site of an enzyme, alters its atoms and electrons in some oxidation-reduc- conditions. kinetic characteristics. tion reactions. metabolomics: The systematic characteriza- molar solution: One mole of solute dissolved NaϩKϩ ATPase: The electrogenic ATP-driven tion of the metabolome of a cell or tissue. in water to give a total volume of 1,000 mL. active transporter in the plasma membrane ϩ metabolon: A supramolecular assembly of mole: One gram molecular weight of a com- of most animal cells that pumps three Na ϩ sequential metabolic enzymes. pound. See also Avogadro’s number. outward for every two K moved inward. metalloprotein: A protein with a metal ion as monocistronic mRNA: An mRNA that can be native conformation: The biologically active its prosthetic group. translated into only one protein. conformation of a macromolecule. metamerism: Division of the body into seg- monoclonal antibodies: Antibodies pro- ncRNA (noncoding RNA): Any RNA that ments, as in insects, for example. duced by a cloned hybridoma cell, which does not encode instructions for a protein micelle: An aggregate of amphipathic mol- therefore are identical and directed against product. ecules in water, with the nonpolar portions the same epitope of the antigen. (Hybridoma negative cooperativity: A property of some in the interior and the polar portions at the cells are stable antibody-producing cell lines multisubunit enzymes or proteins in which exterior surface, exposed to water. that grow well in tissue culture; created by binding of a ligand or substrate to one subunit fusing an antibody-producing B cell with a Michaelis constant (K ): The substrate impairs binding to another subunit. m myeloma cell.) concentration at which an enzyme-catalyzed negative feedback: Regulation of a bio- reaction proceeds at one-half its maximum monosaccharide: A carbohydrate consisting chemical pathway in which a reaction product velocity. of a single sugar unit. inhibits an earlier step in the pathway. Michaelis-Menten equation: The equa- moonlighting enzymes: Enzymes that play neuron: A cell of nervous tissue specialized tion describing the hyperbolic dependence of two distinct roles, at least one of which is for transmission of a nerve impulse. catalytic; the other may be catalytic, regula- the initial reaction velocity, V0, on substrate neurotransmitter: A low molecular weight concentration, [S], in many enzyme-catalyzed tory, or structural. compound (usually containing nitrogen) reactions: motif: Any distinct folding pattern for ele- secreted from the axon terminal of a neuron Vmax[S] ments of secondary structure, observed in one and bound by a specifi c receptor on the next V0 5 . Km 1 [S] or more proteins. A motif can be simple or neuron or on a myocyte; serves to transmit a Michaelis-Menten kinetics: A kinetic pat- complex, and can represent all or just a small nerve impulse. tern in which the initial rate of an enzyme- part of a polypeptide chain. Also called a fold nitrogenase complex: A system of enzymes catalyzed reaction exhibits a hyperbolic or supersecondary structure. capable of reducing atmospheric nitrogen to dependence on substrate concentration. mRNA: See messenger RNA. ammonia in the presence of ATP. microRNA: A class of small RNA molecules mTORC1 (mechanistic target of rapamy- nitrogen cycle: The cycling of various forms (20 to 25 nucleotides after processing is com- cin complex 1): A multiprotein complex of of biologically available nitrogen through plete) involved in gene silencing by inhibiting mTOR (mechanistic target of rapamycin) and the plant, animal, and microbial worlds, and translation and/or promoting the degradation several regulatory subunits, which together through the atmosphere and geosphere. of particular mRNAs. have activity as a Ser/Thr protein kinase. nitrogen fi xation: Conversion of atmospher- Stimulated by nutrients and energy-suffi cient microsomes: Membranous vesicles formed by ic nitrogen (N2) into a reduced, biologically fragmentation of the endoplasmic reticulum conditions, it triggers cell growth and available form by nitrogen-fi xing organisms. of eukaryotic cells; recovered by differential proliferation. NMR: See nuclear magnetic resonance centrifugation. mucopolysaccharide: See glycosaminoglycan. spectroscopy. miRNA: See microRNA. multidrug transporters: Plasma membrane noncoding RNA: See ncRNA. mismatch: A base pair in a nucleic acid that transporters in the ABC transporter family noncyclic electron fl ow: The light-induced cannot form a normal Watson-Crick pair. that expel several commonly used antitumor fl ow of electrons from water to NADPϩ in drugs, thereby interfering with antitumor mismatch repair: An enzymatic system for oxygen-evolving photosynthesis; involves both therapy. repairing base mismatches in DNA. photosystems I and II. multienzyme system: A group of related mitochondrion: Membrane-bounded organ- nonessential amino acids: Amino acids that enzymes participating in a given metabolic elle of eukaryotic cells; contains the enzyme can be made by humans and other vertebrates pathway. systems required for the citric acid cycle, fatty from simpler precursors and are thus not acid oxidation, electron transfer, and oxidative mutarotation: The change in specifi c rotation required in the diet. phosphorylation. of a pyranose or furanose sugar or glycoside nonheme iron proteins: Proteins, usually accompanying the equilibration of its ␣- and mitosis: In eukaryotic cells, the multistep acting in oxidation-reduction reactions, con- ␤-anomeric forms. process that results in the replication of chro- taining iron but no porphyrin groups. mosomes and cell division. mutases: Enzymes that catalyze the transpo- nonpolar: Hydrophobic; describes molecules mixed-function oxygenases: Enzymes (a sition of functional groups. or groups that are poorly soluble in water. monooxygenase, for example) that catalyze mutation: An inheritable change in the nonsense codon: A codon that does not reactions in which two reductants—one of nucleotide sequence of a chromosome. specify an amino acid, but signals the termina- which is generally NADPH, the other the myocyte: A muscle cell. tion of a polypeptide chain. 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Glossary G-11

nonsense mutation: A mutation that results oligomeric protein: A multisubunit protein oxidation-reduction reaction: A reaction in in the premature termination of a polypeptide having two or more identical polypeptide chains. which electrons are transferred from a donor chain. oligonucleotide: A short polymer of nucleo- to an acceptor molecule; also called a redox nonsense suppressor: A mutation, usually in tides (usually fewer than 50). reaction. the gene for a tRNA, that causes an amino acid oligopeptide: A few amino acids joined by oxidative phosphorylation: The enzymatic to be inserted into a polypeptide in response peptide bonds. phosphorylation of ADP to ATP coupled to to a termination codon. oligosaccharide: Several monosaccharide electron transfer from a substrate to molecular nontemplate strand: See coding strand. groups joined by glycosidic bonds. oxygen. nuclear magnetic resonance (NMR) spec- ␻ oxidation: An alternative mode of fatty oxidizing agent (oxidant): The acceptor of troscopy: A technique that utilizes certain acid oxidation in which the initial oxidation is electrons in an oxidation-reduction reaction. quantum mechanical properties of atomic at the carbon most distant from the carboxyl oxygenases: Enzymes that catalyze reactions nuclei to study the structure and dynamics of carbon; as distinct from ␤ oxidation. in which oxygen atoms are directly incorpo- the molecules of which they are a part. oncogene: A cancer-causing gene; any of sev- rated into the product, forming a hydroxyl or nucleases: Enzymes that hydrolyze the eral mutant genes that cause cells to exhibit carboxyl group. In reactions catalyzed by a internucleotide (phosphodiester) linkages of rapid, uncontrolled proliferation. See also monooxygenase, only one of the two O atoms nucleic acids. proto-oncogene. is incorporated; the other is reduced to H2O. nucleic acids: Biologically occurring poly- open reading frame (ORF): A group of con- In reactions catalyzed by a dioxygenase, both nucleotides in which the nucleotide residues tiguous nonoverlapping nucleotide codons in a O atoms are incorporated into the product. are linked in a specifi c sequence by phospho- DNA or RNA molecule that does not include a Compare oxidases. diester bonds; DNA and RNA. termination codon. oxygenic photosynthesis: Light-driven ATP nucleoid: In bacteria, the nuclear zone that open system: A system that exchanges mat- and NADPH synthesis in organisms that use contains the chromosome but has no sur- ter and energy with its surroundings. See also water as the electron source, producing O2. rounding membrane. system. nucleolus: In eukaryotic cells, a densely stain- p operator: A region of DNA that interacts with palindrome: A segment of duplex DNA in ing structure in the nucleus; involved in rRNA a repressor protein to control the expression synthesis and ribosome formation. which the base sequences of the two strands ex- of a gene or group of genes. hibit twofold rotational symmetry about an axis. nucleophile: An electron-rich group with operon: A unit of genetic expression consist- a strong tendency to donate electrons to an paradigm: In biochemistry, an experimental ing of one or more related genes and the model or example. electron-defi cient nucleus (electrophile); the operator and promoter sequences that regu- paralogs: Genes or proteins present in the entering reactant in a bimolecular substitution late their transcription. reaction. same species that possess a clear sequence opsin: The protein portion of the visual and functional relationship to each other. nucleoplasm: The portion of a eukaryotic pigment, which becomes rhodopsin with the partition coeffi cient: A constant that cell’s contents enclosed by the nuclear mem- addition of the chromophore retinal. brane. expresses the ratio in which a given solute optical activity: The capacity of a substance will be partitioned or distributed between two nucleoside: A compound consisting of a to rotate the plane of plane-polarized light. purine or pyrimidine base covalently linked to given immiscible liquids at equilibrium. a pentose. optimum pH: The characteristic pH at which passive transport: Diffusion of a polar sub- an enzyme has maximal catalytic activity. nucleoside diphosphate kinase: An enzyme stance across a biological membrane through that catalyzes the transfer of the terminal orexigenic: Tending to increase appetite and a protein transporter; also called facilitated phosphate of a nucleoside 59-triphosphate to a food consumption. diffusion. nucleoside 59-diphosphate. ORF: See open reading frame. pathogenic: Disease-causing. nucleoside diphosphate sugar: A coen- organelles: Membrane-bounded structures PCR: See polymerase chain reaction. zymelike carrier of a sugar molecule, function- found in eukaryotic cells; contain enzymes and PDB (Protein Data Bank): An international ing in the enzymatic synthesis of polysaccha- other components required for specialized cell database (www.pdb.org) that archives the data rides and sugar derivatives. functions. describing the three-dimensional structure of nucleoside monophosphate kinase: An origin: The nucleotide sequence or site in nearly all macromolecules for which structures enzyme that catalyzes the transfer of the DNA where DNA replication is initiated. have been published. terminal phosphate of ATP to a nucleoside orthologs: Genes or proteins from different pentose: A simple sugar with a backbone 59-monophosphate. species that possess a clear sequence and containing fi ve carbon atoms. nucleosome: In eukaryotes, structural unit functional relationship to each other. pentose phosphate pathway: A pathway for packaging chromatin; consists of a DNA osmosis: Bulk fl ow of water through a semi- present in most organisms that serves to strand wound around a histone core. permeable membrane into another aqueous interconvert hexoses and pentoses and is nucleotide: A nucleoside phosphorylated at compartment containing solute at a higher a source of reducing equivalents (NADPH) one of its pentose hydroxyl groups. concentration. and pentoses for biosynthetic processes; it nucleus: In eukaryotes, a membrane-bounded osmotic pressure: Pressure generated by begins with glucose 6-phosphate and includes organelle that contains chromosomes. the osmotic fl ow of water through a semi- 6-phosphogluconate as an intermediate. Also permeable membrane into an aqueous called the phosphogluconate pathway and the o compartment containing solute at a higher hexose monophosphate pathway. O-glycosidic bonds: Bonds between a sugar concentration. peptidases: Enzymes that hydrolyze peptide and another molecule (typically an alcohol, oxidases: Enzymes that catalyze oxidation bonds. purine, pyrimidine, or sugar) through an inter- reactions in which molecular oxygen serves peptide: Two or more amino acids covalently vening oxygen. as the electron acceptor, but neither of the joined by peptide bonds. oligomer: A short polymer, usually of amino oxygen atoms is incorporated into the product. peptide bond: A substituted amide linkage acids, sugars, or nucleotides; the defi nition Compare oxygenases. between the ␣-amino group of one amino acid of “short” is somewhat arbitrary, but usually oxidation: The loss of electrons from a and the ␣-carboxyl group of another, with the fewer than 50 subunits. compound. elimination of the elements of water. BMGlossary.indd Page G-12 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-12 Glossary

peptidoglycan: A major component of bacte- photosynthetic phosphorylation: See polynucleotide: A covalently linked sequence rial cell walls; generally consists of parallel photophosphorylation. of nucleotides in which the 39 hydroxyl of the heteropolysaccharides cross-linked by short photosystem: In photosynthetic cells, a pentose of one nucleotide residue is joined by peptides. functional set of light-absorbing pigments and a phosphodiester bond to the 59 hydroxyl of peptidyl transferase: The enzyme activity its reaction center, where the energy of an the pentose of the next residue. that synthesizes the peptide bonds of proteins; absorbed photon is transduced into a separa- polypeptide: A long chain of amino acids a ribozyme, part of the rRNA of the large tion of electric charges. linked by peptide bonds; the molecular weight ribosomal subunit. phototroph: An organism that can use the is generally less than 10,000. peripheral proteins: Proteins loosely or energy of light to synthesize its own fuels from polyribosome: See polysome. reversibly bound to a membrane by hydrogen simple molecules such as carbon dioxide, oxy- polysaccharide: A linear or branched bonds or electrostatic forces; generally water gen, and water; as distinct from a chemotroph. polymer of monosaccharide units linked by soluble once released from the membrane. pI: See isoelectric pH. glycosidic bonds. Compare integral proteins. pKa: The negative logarithm of an equilibrium polysome: A complex of an mRNA molecule permeases: See transporters. constant. and two or more ribosomes; also called poly- peroxisome: Membrane-bounded organelle plasmalogen: A phospholipid with an alkenyl ribosome. of eukaryotic cells; contains peroxide-forming ether substituent on C-1 of glycerol. polyunsaturated fatty acid: See PUFA. and peroxide-destroying enzymes. plasma membrane: The exterior membrane P/O ratio: The number of moles of ATP peroxisome proliferator-activated surrounding the cytoplasm of a cell. 1 formed in oxidative phosphorylation per 2O2 receptor: See PPAR. plasma proteins: The proteins present in reduced (thus, per pair of electrons passed to pH: The negative logarithm of the hydrogen blood plasma. O2). Experimental values used in this text are ion concentration of an aqueous solution. plasmid: An extrachromosomal, independently 2.5 for passage of electrons from NADH to O2, phage: See bacteriophage. replicating, small circular DNA molecule; com- and 1.5 for passage of electrons from FADH phenotype: The observable characteristics of monly employed in genetic engineering. to O2. an organism. plastid: In plants, a self-replicating organ- porphyria: Inherited condition resulting from phosphatases: Enzymes that cleave phos- elle; may differentiate into a chloroplast or the lack of one or more enzymes required to phate esters by hydrolysis, the addition of the amyloplast. synthesize porphyrins. elements of water. platelets: Small, enucleated cells that initiate porphyrin: Complex nitrogenous compound phosphodiester linkage: A chemical group- blood clotting; they arise from bone marrow containing four substituted pyrroles covalently ing that contains two alcohols esterifi ed to cells called megakaryocytes. Also known as joined into a ring; often complexed with a one molecule of phosphoric acid, which thus thrombocytes. central metal atom. serves as a bridge between them. pleated sheet: The side-by-side, hydrogen- positive cooperativity: A property of some phosphogluconate pathway: See pentose bonded arrangement of polypeptide chains in multisubunit enzymes or proteins in which phosphate pathway. the extended ␤ conformation. binding of a ligand or substrate to one subunit phospholipid: A lipid containing one or more plectonemic: Describes a structure in a facilitates binding to another subunit. phosphate groups. molecular polymer that has a net twisting of positive-inside rule: General observation that phosphorolysis: Cleavage of a compound strands about each other in some simple and most plasma membrane proteins are oriented with phosphate as the attacking group; analo- regular way. so that most of their positively charged residues gous to hydrolysis. PLP: See pyridoxal phosphate. (Lys and Arg) are on the cytosolic face. phosphorylases: Enzymes that catalyze polar: Hydrophilic, or “water-loving”; describes posttranscriptional processing: The phosphorolysis. molecules or groups that are soluble in water. enzymatic processing of the primary RNA phosphorylation: Formation of a phosphate polarity: (1) In chemistry, the nonuniform transcript to produce functional RNAs, includ- derivative of a biomolecule, usually by enzy- distribution of electrons in a molecule; polar ing mRNAs, tRNAs, rRNAs, and many other matic transfer of a phosphoryl group from ATP. molecules are usually soluble in water. (2) In classes of RNAs.

phosphorylation potential (DGp): The molecular biology, the distinction between the posttranslational modifi cation: Enzymatic actual free-energy change of ATP hydrolysis 59 and 39 ends of nucleic acids. processing of a polypeptide chain after transla- under the nonstandard conditions prevailing poly(A) tail: A length of adenosine residues tion from its mRNA. in a cell. added to the 39 end of many mRNAs in eukary- PPAR (peroxisome proliferator-activated photochemical reaction center: The part of otes (and sometimes in bacteria). receptor): A family of nuclear transcription a photosynthetic complex where the energy of polycistronic mRNA: A contiguous mRNA factors, activated by lipidic ligands, that alter an absorbed photon causes charge separation, with more than two genes that can be trans- the expression of specifi c genes, including initiating electron transfer. lated into proteins. those encoding enzymes of lipid synthesis and photon: The ultimate unit (a quantum) of polyclonal antibodies: A heterogeneous breakdown. light energy. pool of antibodies produced in an animal by primary structure: A description of the cova- photophosphorylation: The enzymatic different B lymphocytes in response to an anti- lent backbone of a polymer (macromolecule), formation of ATP from ADP coupled to the gen. Different antibodies in the pool recognize including the sequence of monomeric subunits light-dependent transfer of electrons in photo- different parts of the antigen. and any interchain and intrachain covalent synthetic cells. polylinker: A short, often synthetic, fragment bonds. photoreduction: The light-induced reduction of DNA containing recognition sequences for primary transcript: The immediate RNA of an electron acceptor in photosynthetic cells. several restriction endonucleases. product of transcription before any posttran- photorespiration: Oxygen consumption oc- polymerase chain reaction (PCR): A repeti- scriptional processing reactions. curring in illuminated temperate-zone plants, tive laboratory procedure that results in a geo- primases: Enzymes that catalyze the forma- largely due to oxidation of phosphoglycolate. metric amplifi cation of a specifi c DNA sequence. tion of RNA oligonucleotides used as primers photosynthesis: The use of light energy to polymorphic: Describes a protein for which by DNA polymerases. produce carbohydrates from carbon dioxide amino acid sequence variants exist in a popu- primer: A short oligomer (of sugars or nucleo- and a reducing agent such as water. Compare lation of organisms, but the variations do not tides, for example) to which an enzyme adds oxygenic photosynthesis. destroy the protein’s function. additional monomeric subunits. BMGlossary.indd Page G-13 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-13

primer terminus: The end of a primer to protein targeting: The process by which much of the amplifi ed template was in the which monomeric subunits are added. newly synthesized proteins are sorted and original sample. priming: (1) In protein phosphorylation, the transported to their proper locations in the cell. quantum: The ultimate unit of energy. phosphorylation of an amino acid residue that proteoglycan: A hybrid macromolecule quaternary structure: The three- becomes the binding site and point of reference consisting of a heteropolysaccharide joined to dimensional structure of a multisubunit for phosphorylation of other residues in the a polypeptide; the polysaccharide is the major protein, particularly the manner in which the same protein. (2) In DNA replication, the syn- component. subunits fi t together. thesis of a short oligonucleotide to which DNA proteome: The full complement of proteins polymerases can add additional nucleotides. expressed in a given cell, or the complete r primosome: An enzyme complex that synthe- complement of proteins that can be expressed racemic mixture (racemate): An equimolar sizes the primers required for lagging strand by a given genome. mixture of the D and L stereoisomers of an DNA synthesis. proteomics: Broadly, the study of the protein optically active compound. processivity: For any enzyme that catalyzes complement of a cell or organism. radical: An atom or group of atoms possessing the synthesis of a biological polymer, the prop- proteostasis: The maintenance of a cellular an unpaired electron; also called a free radical. erty of adding multiple subunits to the poly- steady-state collection of proteins that are mer without dissociating from the substrate. radioactive isotope: An isotopic form of an required for cell functions under a given set of element with an unstable nucleus that stabi- prochiral molecule: A symmetric molecule conditions. lizes itself by emitting ionizing radiation. that can react asymmetrically with an enzyme protomer: A general term describing any radioimmunoassay (RIA): A sensitive, having an asymmetric active site, generating a repeated unit of one or more stably associated chiral product. quantitative method for detecting trace protein subunits in a larger protein structure. amounts of a biomolecule, based on its projection formulas: See Fischer projection If a protomer has multiple subunits, the sub- capacity to displace a radioactive form of the formulas. units may be identical or different. molecule from combination with its specifi c prokaryote: A term used historically to refer proton acceptor: An anionic compound antibody. to any species in the kingdoms Bacteria and capable of accepting a proton from a proton Ras superfamily of G proteins: Small Archaea. The differences between bacteria donor; that is, a base. (formerly referred to as “eubacteria”) and (Mr ~20,000), monomeric guanosine nucleotide– proton donor: The donor of a proton in an binding proteins that regulate signaling and archaea are suffi ciently great that the inclusive acid-base reaction; that is, an acid. term is of marginal usefulness. A tendency membrane traffi cking pathways. Inactive with proton-motive force: The electrochemi- to use “prokaryote” when referring only to GDP bound, they are activated by displace- cal potential inherent in a transmembrane bacteria is common and misleading; “prokary- ment of GDP by GTP, then inactivated by gradient of Hϩ concentration; used in oxidative ote” also implies an ancestral relationship to their intrinsic GTPase. Also called small G phosphorylation and photophosphorylation to eukaryotes, which is incorrect. In this text, proteins. drive ATP synthesis. “prokaryote” and “prokaryotic” are not used. rate constant: The proportionality constant promoter: A DNA sequence at which RNA proto-oncogene: A cellular gene, usually that relates the velocity of a chemical reaction polymerase may bind, leading to initiation of encoding a regulatory protein, that can be to the concentration(s) of the reactant(s). transcription. converted into an oncogene by mutation. rate-limiting step: (1) Generally, the step proofreading: The correction of errors in PUFA (polyunsaturated fatty acid): A in an enzymatic reaction with the greatest the synthesis of an information-containing fatty acid with more than one double bond, activation energy or the transition state of biopolymer by removing incorrect monomeric generally nonconjugated. highest free energy. (2) The slowest step in a subunits after they have been covalently purine: A nitrogenous heterocyclic base found metabolic pathway. added to the growing polymer. in nucleotides and nucleic acids; contains reaction intermediate: Any chemical spe- prostaglandin: One of a class of polyunsatu- fused pyrimidine and imidazole rings. cies in a reaction pathway that has a fi nite rated, cyclic lipids derived from arachidonate puromycin: An antibiotic that inhibits chemical lifetime. that act as paracrine hormones. polypeptide synthesis by being incorporated reactive oxygen species (ROS): Highly prosthetic group: A metal ion or an organic into a growing polypeptide chain, causing its reactive products of the partial reduction premature termination. compound (other than an amino acid) that is of O2, including hydrogen peroxide (H2O2), • 2 covalently bound to a protein and is essential pyridine nucleotide: A nucleotide coenzyme superoxide ( O2 ), and hydroxyl free radical • to its activity. containing the pyridine derivative nicotin- OH, produced as minor byproducts during proteases: Enzymes that catalyze the hydro- amide; NAD or NADP. oxidative phosphorylation. lytic cleavage of peptide bonds in proteins. pyridoxal phosphate (PLP): A coenzyme reading frame: A contiguous, nonoverlapping proteasome: Supramolecular assembly of enzy- containing the vitamin pyridoxine (vitamin set of three-nucleotide codons in DNA or RNA. matic complexes that function in the degrada- B6); functions in reactions involving amino receptor Tyr kinase (RTK): A large family tion of damaged or unneeded cellular proteins. group transfer. of plasma membrane proteins with ligand- protein: A macromolecule composed of pyrimidine: A nitrogenous heterocyclic base binding sites on the extracellular domain, a one or more polypeptide chains, each with a found in nucleotides and nucleic acids. single transmembrane helix, and a cytoplasmic characteristic sequence of amino acids linked pyrimidine dimer: A covalently joined dimer domain with protein Tyr kinase activity con- by peptide bonds. of two adjacent pyrimidine residues in DNA, trolled by the extracellular ligand. Protein Data Bank: See PDB. induced by absorption of UV light; most com- recombinant DNA: DNA formed by the join- protein kinases: Enzymes that transfer the monly derived from two adjacent thymines (a ing of genes into new combinations. terminal phosphoryl group of ATP or another thymine dimer). recombination: Any enzymatic process by nucleoside triphosphate to a Ser, Thr, Tyr, Asp, pyrophosphatase: See inorganic which the linear arrangement of nucleic acid or His side chain in a target protein, thereby pyrophosphatase. sequences in a chromosome is altered by regulating the activity or other properties of cleavage and rejoining. that protein. q recombinational DNA repair: Recombi- protein phosphatases: Enzymes that hydro- Q: See mass-action ratio. national processes directed at the repair of lyze a phosphate ester or anhydride bond on a quantitative PCR (qPCR): A PCR proce- DNA strand breaks or cross-links, especially at

protein, releasing inorganic phosphate, Pi. dure that allows the determination of how inactivated replication forks. BMGlossary.indd Page G-14 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-14 Glossary

redox pair: An electron donor and its repressible enzyme: In bacteria, an enzyme ribonucleic acid: See RNA. corresponding oxidized form; for example, whose synthesis is inhibited when its reaction ribonucleotide: A nucleotide containing ϩ NADH and NAD . product is readily available to the cell. D-ribose as its pentose component. redox reaction: See oxidation-reduction repression: A decrease in the expression of a ribosomal RNA (rRNA): A class of RNA reaction. gene in response to a change in the activity of molecules serving as components of ribosomes. reducing agent (reductant): The electron a regulatory protein. ribosome: A supramolecular complex of donor in an oxidation-reduction reaction. repressor: The protein that binds to the rRNAs and proteins, approximately 18 to 22 reducing end: The end of a polysaccharide regulatory sequence or operator for a gene, nm in diameter; the site of protein synthesis. having a terminal sugar with a free anomeric blocking its transcription. riboswitch: A structured segment of an carbon; the terminal residue can act as a residue: A single unit in a polymer; for exam- mRNA that binds to a specifi c ligand and reducing sugar. ple, an amino acid in a polypeptide chain. The affects the translation or processing of the reducing equivalent: A general term for an term refl ects the fact that sugars, nucleotides, mRNA. electron or an electron equivalent in the form and amino acids lose a few atoms (generally ribozymes: Ribonucleic acid molecules with of a hydrogen atom or a hydride ion. the elements of water) when incorporated in catalytic activities; RNA enzymes. their respective polymers. reducing sugar: A sugar in which the car- ribulose 1,5-bisphosphate carboxylase/ bonyl (anomeric) carbon is not involved in a respiration: Any metabolic process that leads oxygenase (rubisco): The enzyme that fi xes glycosidic bond and can therefore undergo to the uptake of oxygen and the release of CO . 2 inorganic CO2 into organic form (3-phospho- oxidation. respiration-linked phosphorylation: ATP glycerate) in those organisms (plants and

reduction: The gain of electrons by a com- formation from ADP and Pi, driven by electron some microorganisms) capable of CO2 fi xation. pound or ion. fl ow through a series of membrane-bound Rieske iron-sulfur protein: A type of iron- regulator of G protein signaling (RGS): carriers, with a proton gradient as the direct sulfur protein in which two of the ligands to Protein structural domain that stimulates the source of energy driving rotational catalysis by the central iron ion are His side chains; act in GTPase activity of heterotrimeric G proteins. ATP synthase. many electron-transfer sequences, including regulatory cascade: A multistep regulatory respiratory chain: The electron-transfer oxidative phosphorylation and photophos- pathway in which a signal leads to activation chain; a sequence of electron-carrying proteins phorylation. of a series of proteins in succession, with each that transfers electrons from substrates to RNA (ribonucleic acid): A polyribonucleo- protein in the succession catalytically activat- molecular oxygen in aerobic cells. tide of a specifi c sequence linked by succes- ing the next, such that the original signal is response element: A region of DNA, near sive 39,59-phosphodiester bonds. amplifi ed exponentially. (upstream from) a gene, that is bound by RNA editing: Posttranscriptional modifi cation regulatory enzyme: An enzyme with a specifi c proteins that infl uence the rate of of an mRNA that alters the meaning of one or regulatory function, through its capacity to transcription of the gene. more codons during translation. undergo a change in catalytic activity by allo- restriction endonucleases: Site-specifi c RNA polymerase: An enzyme that catalyzes steric mechanisms or by covalent modifi cation. endodeoxyribonucleases that cleave both the formation of RNA from ribonucleoside regulatory gene: A gene that gives rise to strands of DNA at points in or near the specifi c 59-triphosphates, using a strand of DNA or a product involved in the regulation of the site recognized by the enzyme; important tools RNA as a template. expression of another gene; for example, a in genetic engineering. RNA splicing: Removal of introns and joining gene encoding a repressor protein. restriction fragment: A segment of double- of exons in a primary transcript. regulatory sequence: A DNA sequence stranded DNA produced by the action of a ROS: See reactive oxygen species. involved in regulating the expression of a restriction endonuclease on a larger DNA. rRNA: See ribosomal RNA. gene; for example, a promoter or operator. retinal: A 20-carbon isoprene aldehyde RTK: See receptor Tyr kinase. regulon: A group of genes or operons that are derived from carotene, which serves as rubisco: See ribulose 1,5-bisphosphate coordinately regulated even though some, or the light-sensitive component of the visual carboxylase/oxygenase. all, may be spatially distant in the chromosome pigment rhodopsin. Illumination converts or genome. 11-cis-retinal to all-trans-retinal. relaxed DNA: Any DNA that exists in its retrovirus: An RNA virus containing a s most stable and unstrained structure, typically reverse transcriptase. salvage pathway: Pathway for synthesis of a the B form under most cellular conditions. biomolecule, such as a nucleotide, from inter- reverse transcriptase: An RNA-directed mediates in the degradative pathway for the release factors: Protein factors of the cytosol DNA polymerase in retroviruses; capable of biomolecule; a recycling pathway, as distinct required for the release of a completed poly- making DNA complementary to an RNA. peptide chain from a ribosome; also known as from a de novo pathway. reversible inhibition: Inhibition by a termination factors. sarcomere: A functional and structural unit of molecule that binds reversibly to the enzyme, renaturation: Refolding of an unfolded the muscle contractile system. such that the enzyme activity returns when (denatured) globular protein so as to restore the inhibitor is no longer present. satellite DNA: Highly repeated, nontrans- its native structure and function. lated segments of DNA in eukaryotic R group: (1) Formally, an abbreviation denot- replication: Synthesis of daughter nucleic chromosomes; most often associated with the ing any alkyl group. (2) Occasionally, used in acid molecules identical to the parental centromeric region. Its function is unknown. a more general sense to denote virtually any nucleic acid. Also called simple-sequence DNA. organic substituent (the R groups of amino replication fork: The Y-shaped structure acids, for example). saturated fatty acid: A fatty acid containing generally found at the point where DNA is a fully saturated alkyl chain. RGS: See regulator of G protein signaling being synthesized. scaffold proteins: Noncatalytic proteins that replicative form: Any of the full-length rhodopsin: The visual pigment, composed of nucleate formation of multienzyme complexes structural forms of a viral chromosome that the protein opsin and the chromophore retinal. by providing two or more specifi c binding sites serve as distinct replication intermediates. RIA: See radioimmunoassay. for those proteins. replisome: The multiprotein complex that ribonuclease: A nuclease that catalyzes the scramblases: Membrane proteins that cata- promotes DNA synthesis at the replication hydrolysis of certain internucleotide linkages lyze the movement of phospholipids across fork. of RNA. the membrane bilayer, leading to uniform BMGlossary.indd Page G-15 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-15

distribution of a lipid between the two mem- signal transduction: The process by which sphingolipid: An amphipathic lipid with a brane leafl ets. an extracellular signal (chemical, mechanical, sphingosine backbone to which are attached a secondary metabolism: Pathways that lead or electrical) is amplifi ed and converted to a long-chain fatty acid and a polar alcohol. to specialized products not found in every cellular response. spliceosome: A complex of RNAs and living cell. silent mutation: A mutation in a gene that proteins involved in the splicing of mRNAs in secondary structure: The local spatial causes no detectable change in the biological eukaryotic cells. arrangement of the main-chain atoms in a characteristics of the gene product. splicing: See RNA splicing. segment of a polypeptide chain; also applied to simple diffusion: The movement of solute standard free-energy change (DG8): The polynucleotide structure. molecules across a membrane to a region of free-energy change for a reaction occurring second law of thermodynamics: The law lower concentration, unassisted by a protein under a set of standard conditions: tempera- stating that, in any chemical or physical transporter. ture, 298 K; pressure, 1 atm or 101.3 kPa; and process, the entropy of the universe tends to simple protein: A protein yielding only amino all solutes at 1 M concentration. DG98 denotes increase. acids on hydrolysis. the standard free-energy change at pH 7.0 in second messenger: An effector molecule simple sequence DNA: See satellite DNA. 55.5 M water. synthesized in a cell in response to an external single nucleotide polymorphism (SNP): A standard reduction potential (E98): The signal (fi rst messenger) such as a hormone. genomic base-pair change that helps distin- electromotive force exhibited at an electrode sedimentation coeffi cient: A physical con- guish one species from another or one subset by 1 M concentrations of a reducing agent and 8 stant specifying the rate of sedimentation of of individuals in a population. its oxidized form at 25 C and pH 7.0; a mea- a particle in a centrifugal fi eld under specifi ed sure of the relative tendency of the reducing site-directed mutagenesis: A set of meth- agent to lose electrons. conditions. ods used to create specifi c alterations in the statin: Any of a class of drugs used to reduce selectins: A large family of membrane sequence of a gene. blood cholesterol in humans; act by inhibiting proteins, lectins that bind oligosaccharides on site-specifi c recombination: A type of other cells tightly and specifi cally and serve to the enzyme HMG-CoA reductase, an early step genetic recombination that occurs only at in sterol synthesis. carry signals across the plasma membrane. specifi c sequences. SELEX: A method for rapid experimental steady state: A nonequilibrium state of a size-exclusion chromatography: A proce- system through which matter is fl owing and identifi cation of nucleic acid sequences (usu- dure for the separation of molecules by size, ally RNA) that have particular catalytic or in which all components remain at a constant based on the capacity of porous polymers concentration. ligand-binding properties. to exclude solutes above a certain size; also stem cells: The common, self-regenerating sequence polymorphisms: Any alterations in called gel fi ltration. genomic sequence (base-pair changes, inser- cells in bone marrow that give rise to differ- small G proteins: See Ras superfamily of G entiated blood cells such as erythrocytes and tions, deletions, rearrangements) that help proteins. distinguish subsets of individuals in a popula- lymphocytes. tion or distinguish one species from another. small nuclear RNA (snRNA): A class of stereoisomers: Compounds that have the short RNAs, typically 100 to 200 nucleotides serine proteases: One of four major classes same composition and the same order of long, found in the nucleus and involved in the of proteases, featuring a reaction mechanism atomic connections but different molecular splicing of eukaryotic mRNAs. in which an active-site Ser residue acts as a arrangements. covalent catalyst. small nucleolar RNA (snoRNA): A class of sterol: A lipid containing the steroid nucleus. short RNAs, generally 60 to 300 nucleotides Shine-Dalgarno sequence: A sequence in sticky ends: Two DNA ends in the same DNA long, that guide the modifi cation of rRNAs in an mRNA that is required for binding bacterial molecule, or in different molecules, with short the nucleolus. ribosomes. overhanging single-stranded segments that SNP: See single nucleotide polymorphism. are complementary to one another, facilitating short tandem repeat (STR): A short (typi- ligation of the ends; also known as cohesive cally 3 to 6 bp) DNA sequence, repeated many somatic cells: All body cells except the germ- ends. times in tandem at a particular location in a line cells. chromosome. SOS response: In bacteria, a coordinated stimulatory G protein (Gs): A trimeric regulatory GTP-binding protein that, when SH2 domain: A protein domain that binds induction of a variety of genes in response to activated by an associated plasma membrane tightly to a phosphotyrosine residue in certain high levels of DNA damage. receptor, stimulates a neighboring membrane proteins such as the receptor Tyr kinases, initi- Southern blot: A DNA hybridization pro- enzyme such as adenylyl cyclase. Its effects ating the formation of a multiprotein complex cedure in which one or more specifi c DNA oppose those of G . that acts in a signaling pathway. fragments are detected in a larger population i stop codons: See termination codons. shuttle vector: A recombinant DNA vector by hybridization to a complementary, labeled that can be replicated in two or more different nucleic acid probe. STR: See short tandem repeat. host species. See also vector. specifi c acid-base catalysis: Acid or base stroma: The space and aqueous solution sickle-cell anemia: A human disease char- catalysis involving the constituents of water enclosed within the inner membrane of a acterized by defective hemoglobin molecules (hydroxide or hydronium ions). chloroplast, not including the contents in the in individuals homozygous for a mutant allele specifi c activity: The number of micromoles thylakoid membranes. coding for the ␤ chain of hemoglobin. (␮mol) of a substrate transformed by an en- structural gene: A gene coding for a protein ␴: (1) See superhelical density. (2) A subunit zyme preparation per minute per milligram of or RNA molecule; as distinct from a regulatory of the bacterial RNA polymerase that confers protein at 25 8C; a measure of enzyme purity. gene. specifi ty for certain promoters; usually specifi city: The ability of an enzyme or substitution mutation: A mutation caused designated by a superscript indicating its size receptor to discriminate among competing by the replacement of one base by another. (for example, ␴70 has a molecular weight of substrates or ligands. substrate: The specifi c compound acted upon 70,000). specifi c rotation: The rotation, in degrees, by an enzyme. signal sequence: An amino acid sequence, of the plane of plane-polarized light (D-line of substrate channeling: Movement of the often at the amino terminus, that signals the sodium) by an optically active compound at chemical intermediates in a series of enzyme- cellular fate or destination of a newly synthe- 25 8C, with a specifi ed concentration and light catalyzed reactions from the active site of one sized protein. path. enzyme to that of the next enzyme in the BMGlossary.indd Page G-16 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

G-16 Glossary

pathway, without leaving the surface of a pro- template strand: A strand of nucleic acid topology: The study of the properties of an tein complex that includes both enzymes. used by a polymerase as a template to synthe- object that do not change under continuous substrate-level phosphorylation: Phos- size a complementary strand, as distinct from deformations such as twisting or bending. phorylation of ADP or some other nucleoside the coding strand. TPP: See thiamine pyrophosphate. 59-diphosphate coupled to the dehydrogena- terminal transferase: An enzyme that cata- trace element: A chemical element required tion of an organic substrate; independent of lyzes the addition of nucleotide residues of a by an organism in only trace amounts. 9 the electron-transfer chain. single kind to the 3 end of DNA chains. transaminases: See aminotransferases. suicide inactivator: A relatively inert termination codons: UAA, UAG, and UGA; transamination: Enzymatic transfer of an molecule that is transformed by an enzyme, at in protein synthesis, these codons signal amino group from an ␣-amino acid to an its active site, into a reactive substance that the termination of a polypeptide chain. Also ␣-keto acid. irreversibly inactivates the enzyme. known as stop codons. transcription: The enzymatic process sulfonylurea drugs: A group of oral medica- termination factors: See release factors. whereby the genetic information contained in tions used in the treatment of type 2 diabetes; termination sequence: A DNA sequence, at one strand of DNA is used to specify a comple- ϩ ␤ act by closing K channels in pancreatic the end of a transcriptional unit, that signals mentary sequence of bases in an mRNA chain. cells, stimulating insulin secretion. the end of transcription. transcriptional control: The regulation of a supercoil: The twisting of a helical (coiled) tertiary structure: The three-dimensional protein’s synthesis by regulation of the forma- molecule on itself; a coiled coil. conformation of a polymer in its native folded tion of its mRNA. supercoiled DNA: DNA that twists upon state. transcription factor: In eukaryotes, a itself because it is under- or overwound (and tetrahydrobiopterin: The reduced coen- protein that affects the regulation and tran- thereby strained) relative to B-form DNA. zyme form of biopterin. scription initiation of a gene by binding to a superhelical density (␴): In a helical mol- tetrahydrofolate: The reduced, active coen- regulatory sequence near or within the gene ecule such as DNA, the number of supercoils zyme form of the vitamin folate. and interacting with RNA polymerase and/or (superhelical turns) relative to the number of thermogenesis: The biological generation of other transcription factors. coils (turns) in the relaxed molecule. heat by muscle activity (shivering), uncoupled transcriptome: The entire complement of supersecondary structure: See motif. oxidative phosphorylation, or the operation of RNA transcripts present in a given cell or tis- suppressor mutation: A mutation that futile cycles. sue under specifi c conditions. totally or partially restores a function lost by thermogenin: A protein of the inner mito- transducin: The trimeric G protein activated a primary mutation; located at a site different chondrial membrane in brown adipose tissue when light is absorbed by visual rhodopsin; from the site of the primary mutation. that allows transmembrane movement of activated transducin activates cGMP phospho- Svedberg (S): A unit of measure of the rate protons, short-circuiting the normal use of diesterase. at which a particle sediments in a centrifugal protons to drive ATP synthesis and dissipating transduction: (1) Generally, the conversion fi eld. the energy of substrate oxidation as heat; also of energy or information from one form to called uncoupling protein 1 (UCP1). symbionts: Two or more organisms that are another. (2) The transfer of genetic informa- mutually interdependent; usually living in thiamine pyrophosphate (TPP): The active tion from one cell to another by means of a physical association. coenzyme form of vitamin B1; involved in viral vector. aldehyde transfer reactions. symport: Cotransport of solutes across a transfer RNA (tRNA): A class of RNA mol- membrane in the same direction. thioester: An ester of a carboxylic acid with a ecules (Mr 25,000 to 30,000), each of which thiol or mercaptan. combines covalently with a specifi c amino acid synteny: Conserved gene order along the 9 as the fi rst step in protein synthesis. chromosomes of different species. 3 end: The end of a nucleic acid that lacks a nucleotide bound at the 39 position of the transformation: Introduction of an exog- synthases: Enzymes that catalyze condensa- terminal residue. enous DNA into a cell, causing the cell to tion reactions in which no nucleoside triphos- acquire a new phenotype. phate is required as an energy source. thrombocytes: See platelets. transgenic: Describes an organism that has synthetases: Enzymes that catalyze conden- thromboxane: Any of a class of molecules genes from another organism incorporated in sation reactions using ATP or another nucleo- derived from arachidonate and involved in its genome as a result of recombinant DNA side triphosphate as an energy source. platelet aggregation during blood clotting. procedures. thylakoid: Closed cisterna, or disk, formed system: An isolated collection of matter; all transition state: An activated form of a other matter in the universe apart from the by the pigment-bearing internal membranes of chloroplasts. molecule in which the molecule has undergone system is called the surroundings. a partial chemical reaction; the highest point thymine dimer: See pyrimidine dimer. systems biology: The study of complex on the reaction coordinate. tissue culture: Method by which cells derived biochemical systems, integrating the functions transition-state analog: A stable molecule from multicellular organisms are grown in of several to all of the macromolecules in a cell that resembles the transition state of a partic- liquid media. (RNA, DNA, proteins). ular reaction, and therefore binds the enzyme titration curve: A plot of pH versus the that catalyzes the reaction more tightly than equivalents of base added during titration of does the substrate in the ES complex. an acid. t translation: The process in which the genetic tag: An extra segment of protein that is fused T lymphocyte (T cell): One of a class of information present in an mRNA molecule via modifi cation of its gene to a protein of blood cells (lymphocytes) of thymic origin, specifi es the sequence of amino acids during interest, usually for purposes of purifi cation. involved in cell-mediated immune reactions. protein synthesis. T cell: See T lymphocyte. tocopherol: Any of several forms of vitamin E. translational control: The regulation of a telomere: Specialized nucleic acid structure topoisomerases: Enzymes that introduce protein’s synthesis by regulation of the rate of found at the ends of linear eukaryotic positive or negative supercoils in closed, circu- its translation on the ribosome. chromosomes. lar duplex DNA. translational frameshifting: A programmed template: A macromolecular mold or pattern topoisomers: Different forms of a covalently change in the reading frame during translation for the synthesis of an informational macro- closed, circular DNA molecule that differ only of an mRNA on a ribosome, occurring by any molecule. in their linking number. of several mechanisms. BMGlossary.indd Page G-17 28/09/12 9:29 AM user-F408 /Users/user-F408/Desktop

Glossary G-17

translational repressor: A repressor that response regulator, which, when phosphory- as hormones or neurotransmitters to be moved binds to an mRNA, blocking translation. lated, alters the output of the signaling system. within or out of a cell. translocase: (1) An enzyme that catalyzes u viral vector: A viral DNA altered so that it membrane transport. (2) An enzyme that can act as a vector for recombinant DNA. causes a movement such as the movement of a ubiquitin: A small, highly conserved eukary- virion: A virus particle. ribosome along an mRNA. otic protein that targets an intracellular pro- tein for degradation by proteasomes. Several transpiration: Passage of water from the virus: A self-replicating, infectious, nucleic ubiquitin molecules are covalently attached in roots of a plant to the atmosphere via the vas- acid–protein complex that requires an intact tandem to a Lys residue in the target protein cular system and the stomata of the leaves. host cell for its replication; its genome is either by a specifi c ubiquitinating enzyme. DNA or RNA. transporters: Proteins that span a membrane ultraviolet (UV) radiation: Electromagnetic and transport specifi c nutrients, metabolites, vitamin: An organic substance required in radiation in the region of 200 to 400 nm. ions, or proteins across the membrane; some- small quantities in the diet of some species; times called permeases. uncompetitive inhibition: The reversible generally functions as a component of a inhibition pattern resulting when an inhibitor transposition: The movement of a gene or coenzyme. molecule can bind to the enzyme-substrate set of genes from one site in the genome to complex but not to the free enzyme. v-SNAREs: Protein receptors in the mem- another. brane of a secretory vesicle (typically the uncoupling agent: A substance that un- plasma membrane) that bind to t-SNAREs in transposon (transposable element): A couples phosphorylation of ADP from electron a targeted membrane (typically the plasma segment of DNA that can move from one posi- transfer; for example, 2,4-dinitrophenol. tion in the genome to another. membrane) of a secretory vesicle and mediate uncoupling protein 1: See thermogenin. triacylglycerol: An ester of glycerol with fusion of the vesicle and target membranes. uniport: A transport system that carries only three molecules of fatty acid; also called a one solute, as distinct from cotransport. triglyceride or neutral fat. w unsaturated fatty acid: A fatty acid contain- tricarboxylic acid cycle: See citric acid cycle. Western blotting: See immunoblotting. ing one or more double bonds. white adipose tissue (WAT): Nonthermo- trimeric G proteins: Members of the G urea cycle: A cyclic metabolic pathway in protein family with three subunits, which func- genic adipose tissue rich in triacylglycerols vertebrate liver, synthesizing urea from amino stored and mobilized in response to hormonal tion in a variety of signaling pathways. Inactive groups and carbon dioxide. with GDP bound, they are activated by associ- signals. Transfer of electrons in the mito- ureotelic: Excreting excess nitrogen in the ated receptors as bound GDP is displaced chondrial respiratory chain is tightly coupled form of urea. by GTP, then inactivated by their intrinsic to ATP synthesis. Compare brown adipose GTPase activity. uricotelic: Excreting excess nitrogen in the tissue. form of urate (uric acid). triose: A simple sugar with a backbone con- wild type: The normal (unmutated) genotype or phenotype. taining three carbon atoms. v tRNA: See transfer RNA. wobble: The relatively loose base pairing Vmax: The maximum velocity of an enzymatic between the base at the 39 end of a codon and tropic hormone (tropin): A peptide hor- reaction when the binding site is saturated the complementary base at the 59 end of the mone that stimulates a specifi c target gland to with substrate. anticodon. secrete its hormone; for example, thyrotropin van der Waals interaction: Weak intermo- produced by the pituitary stimulates secretion lecular forces between molecules as a result of x of thyroxine by the thyroid. each inducing polarization in the other. x-ray crystallography: The analysis of x-ray t-SNAREs: Protein receptors in a targeted vector: A DNA molecule known to replicate diffraction patterns of a crystalline compound, membrane (typically the plasma membrane) autonomously in a host cell, to which a seg- used to determine the molecule’s three- that bind to v-SNAREs in the membrane of ment of DNA may be spliced to allow its rep- dimensional structure. a secretory vesicle and mediate fusion of the lication; for example, a plasmid or an artifi cial vesicle and target membranes. chromosome. tumor suppressor gene: One of a class of z genes that encode proteins that normally regu- vectorial: Describes an enzymatic reaction or zinc fi nger: A specialized protein motif late the cell cycle by suppressing cell division. transport process in which the protein has a involved in DNA recognition by some DNA- Mutation of one copy of the gene is usually specifi c orientation in a biological membrane binding proteins; characterized by a single without effect, but when both copies are de- such that the substrate is moved from one atom of zinc coordinated to four Cys residues fective, the cell is allowed to continue dividing side of the membrane to the other as it is or to two His and two Cys residues. without limitation, producing a tumor. converted into product. Z scheme: The path of electrons in oxygenic turnover number: The number of times an vectorial metabolism: Metabolic transforma- photosynthesis from water through photo- enzyme molecule transforms a substrate mol- tions in which the location (not the chemical system II and the cytochrome b6 f complex to ecule per unit time, under conditions giving composition) of a substrate changes relative to photosystem I and fi nally to NADPH. When maximal activity at substrate concentrations the plasma membrane or a membrane between the sequence of electron carriers is plotted that are saturating. two cellular compartments. Transporters against their reduction potentials, the path of two-component signaling systems: Signal- catalyze vectorial reactions, as do the proton electrons looks like a sideways Z. transducing systems found in bacteria and pumps of oxidative phosphorylation and pho- zwitterion: A dipolar ion with spatially sepa- plants, composed of a receptor His kinase that tophosphorylation. rated positive and negative charges. phosphorylates an internal His residue when vesicle: A small, spherical membrane- zymogen: An inactive precursor of an enzyme; occupied by its ligand. It then catalyzes phos- bounded particle with an internal aqueous for example, pepsinogen, the precursor of phoryl transfer to a second component, the compartment that contains components such pepsin. this page left intentionally blank BMCredits.indd Page 2 22/10/12 10:50 AM user-F408 /Users/user-F408/Desktop

Credits

Molecular Models and two liganded T-state haemoglobins: T(␣-oxy) haemoglobin and T(met) haemoglobin. J. Mol. Biol. 228, 551; p. 98 (Sanger) UPI/Corbis-Bettmann; MOLECULAR GRAPHICS Unless indicated, all molecular graphics were Figures 3–30 Adapted from Mann, M. & Wilm, M. (1995) Electrospray mass produced by H. Adam Steinberg, artforscience.com, or Jean-Yves Sgro, Ph.D., spectrometry for protein characterization. Trends Biochem. Sci. 20, 219; University of Wisconsin–Madison, Biotechnology Center. Figure 3–31a Adapted from Keough, T., Youngquist, R.S., & Lacey, M.P. (1999) ATOMIC COORDINATES Unless indicated, all atomic coordinates were A method for high-sensitivity peptide sequencing using postsource decay obtained from the Research Collaboratory for Structural Bioinformatics matrix-assisted laser desorption ionization mass spectrometry. Proc. Natl. Acad. (RCSB) Protein Data Bank (PDB), www.pdb.org. See Berman, H.M., Sci. 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Sybyl 6.2, Tripos Inc., www.tripos.com; Visual Molecular Dynamics, www.ks. 14, 1188; Figures 3–33, 3–34, 3–35 Adapted from Gupta, R.S. (1998) Protein uiuc.edu/Research/vmd/; or RasMol, rasmol.org. phylogenies and signature sequences: a reappraisal of evolutionary relationships among archaebacteria, eubacteria, and eukaryotes. Microbiol. Mol. Biol. Rev. CHAPTER 1 Figure 1–1a Dennis Kunkel Microscopy, Inc./Visuals Unlimited; 62, 1435, Figs 2, 7, 11, respectively; Figure 3–36 Adapted from Delsuc, F., Figure 1–1b W. Perry Conway/Corbis; Figure 1–1c Dave Pape/Wikipedia; Brinkmann, H., & Philippe, H. (2005) Phylogenomics and the reconstruction of Figure 1–2 The Bridgeman Art Library; Figure 1–4 Adapted from Woese, the tree of life. Nat. Rev. Genet. 6, 366; p. 113, problem 21, see citation for Box C.R. (1987) Bacterial evolution. Microbiol. Rev. 51, 221, Fig. 4; Figure 1–6a 3–2 Figure 1, document ID PDOC00270; p. 113, problem 22, see citation for David S. 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CHAPTER 10 Figures 10–2a,b, 10–3 Coordinates from Sybyl; Figure 10–4a ATPase structure revisited. Curr. Opin. Struct. Biol. 20, 431, Fig. 1; Figure Dr. Alvin Telser/Visuals Unlimited, Inc.; Figure 10–4b Courtesy of Howard 11–36b PDB ID 1SU4, Toyoshima, C., Nakasako, M., Nomura, H., & Ogawa, H. Goodman, Harvard Medical School, Department of Genetics; Figure 10–6b (2000) Crystal structure of the calcium pump of sarcoplasmic reticulum at 2.6 iStockphoto/Thinkstock; p. 367 (Thudichum) From Drabkin, D.L. (1958) angstrom resolution. Nature 405, 647; Figure 11–36c PDB ID 3KDP, Preben Thudichum: Chemist of the Brain, University of Pennsylvania Press, credited Morth, J., Pedersen, B.P., Toustrup-Jensen, M.S., Sorensen, T.L., Petersen, to Thudichum, J.L.W. (1898) Briefe über öffentliche Gesundheitspfl ege: ihre J., Andersen, J.P., Vilsen, B., & Nissen, P. (2007) Crystal structure of the bisherigen Leistungen und heutigen Aufgaben, F. Pietzcker, Tübingen; Box sodium-potassium pump. 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(1996) 3B8E, see citation for PDB ID 3KDP; p. 411 (Skou) Courtesy of Information Beginners’ guide to mass spectrometry of fatty acids: 2. general purpose Offi ce, University of Aarhus, Denmark; Figure 11–37 Adapted from derivatives. Lipid Technol. 8, 64. Kühlbrandt, W. (2004) Biology, structure and mechanism of P-type ATPases. CHAPTER 11 Figure 11–1 Don W. Fawcett/Photo Researchers; Figure 11–5 Nat. Rev. Mol. Cell Biol. 5, 291; Figure 11–40a PDB ID 3G60, Aller, S.G., Yu, Data from Zachowski, A. (1993) Phospholipids in animal eukaryotic J., Ward, A., Weng, Y., Chittaboina, S., Zhuo, R., Harrell, P.M., Trinh, Y.T., Zhang, membranes: transverse asymmetry and movement. Biochem. J. 294, 1; Q., Urbatsch, I.L., & Chang, G. (2009) Structure of P-glycoprotein reveals a Figure 11–6 Adapted from van Meer, G. & de Kroon, A.I.P.M. (2011) Lipid molecular basis for poly-specifi c drug binding. Science 323, 1718; Figure map of the mammalian cell. J. 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C-8 Credits

CHAPTER 28 p. 1159 (Jacob, Monod) Corbis/Bettmann; Figure 28–8c PDB Winkler, W.C. & Breaker, R.R. (2005) Regulation of bacterial gene expression ID 2PE5, Daber, R., Stayrook, S., Rosenberg, A., & Lewis, M. (2007) Structural by riboswitches. Annu. Rev. Microbiol. 59, 493; Figure 28–25 Eye of Science; analysis of lac repressor bound to allosteric effectors. J. Mol. Biol. 370, 609; Figure 28–28c PDB ID 1QRV, Murphy IV, F.V., Sweet, R.M., & Churchill, M.E. Figure 28–9 Adapted from Huret, J.L. (2006) DNA: molecular structure. Atlas (1999) The structure of a chromosomal high mobility group protein-DNA Genet. Cytogenet. Oncol. Haematol., http://atlasgeneticsoncology.org/Educ/ complex reveals sequence-neutral mechanisms important for non-sequence- DNAEngID30001ES.html; Figure 28–11 PDB ID 2PE5, see citation for Figure specifi c DNA recognition. EMBO J. 18, 6610; Figure 28–29 Adapted from 28–8c; Figure 28–12 PDB ID 1ZAA, Pavletich, N.P. & Pabo, C.O. (1991) Zinc D’Alessio, J.A., Wright, K.J., & Tjian, R. (2009) Shifting players and paradigms fi nger-DNA recognition: crystal structure of a Zif268-DNA complex at 2.1 Å. in cell-specifi c transcription. Mol. Cell 36, 924; Figure 28–33 Schwabe, J.W.R. Science 252, 809; Figure 28–13 PDB ID 1FJL, Wilson, D.S., Guenther, B., & Rhodes, D. (1991) Beyond zinc fi ngers: steroid hormone receptors have a Desplan, C., & Kuriyan, J. (1995) High resolution crystal structure of a paired novel structural motif for DNA recognition. Trends Biochem. Sci. 16, 291; (Pax) class cooperative homeodomain dimer on DNA. Cell 82, 709; Figure p. 1185 (Mello) Courtesy of Craig Mello; (Fire) Linda A. Cicero/Stanford News 28–14a McKnight, S.L. (1991) Molecular zippers in gene regulation. Sci. Am. Service; Figure 28–36 Courtesy of F. R. Turner, Department of Biology, 264 (April), 54–64; Figure 28–14b PDB ID 1YSA, Ellenberger, T.E., Brandl, University of Indiana, Bloomington (late embryo), and Prof. Dr. Christian C.J., Struhl, K., & Harrison, S.C. (1992) The GCN4 basic region leucine zipper Klambt, Westfälische Wilhelms-Universität Münster, Institut für Neuro- und binds DNA as a dimer of uninterrupted ␣ helices: crystal structure of the Verhaltensbiologie (other photos); p. 1187 (Nüsslein-Volhard) Courtesy of protein-DNA complex. Cell 71, 1223; Figure 28–15 PDB ID 1HLO, Brownlie, Christiane Nüsslein-Volhard/Micheline Pelletier; p. 1188 (Lewis) CalTech P., Ceska, T.A., Lamers, M., Romier, C., Theo, H., & Suck, D. (1997) The crystal Archives; (Wieschaus) Courtesy of Eric F. Wieschaus; Figure 28–38 Wolfgang structure of an intact human max-DNA complex: new insights into mechanisms Driever and Christiane Nüsslein-Volhard, Max-Planck-Institut; Figure 28–40a of transcriptional control. Structure 5, 509; Figure 28–16 PDB ID 1RUN, Courtesy of Stephen J. Small, Department of Biology, New York University; Parkinson, G., Gunasekera, A., Vojtechovsky, J., Zhang, X., Kunkel, T.A., Figure 28–40b Courtesy of Phillip Ingham, Imperial Cancer Research Fund, Berman, H., & Ebright, R.H. (1996) Aromatic hydrogen bond in sequence- Oxford University; Figure 28–41a Photo from F. R. Turner, University of specifi c protein-DNA recognition. Nat. Struct. Biol. 3, 837; Figure 28–19a Indiana, Bloomington, Department of Biology; Figure 28–42a,b Photo from Watson, J.D., Hopkins, N.H., Roberts, J.W., Steitz, J.A., & Weiner, A.M. (1987) F. R. Turner, University of Indiana, Bloomington, Department of Biology; Molecular Biology of the Gene, 4th edn, The Benjamin/Cummings Publishing Figure 28–42c,d E. B. Lewis, California Institute of Technology, Division of Company, Menlo Park, CA, p. 487; Figure 28–21 Adapted from Nomura, Biology; p. 1193 (Thomson) Courtesy of James Thomson; Box 28–1 Figure 1 M., Gourse, R., & Baughman, G. (1984) Regulation of the synthesis of ribosomes Adapted from Abzhanov, A., Kuo, W.P., Hartmann, C., Grant, B.R., Grant, P.R., and ribosomal components. Annu. Rev. Biochem. 53, 75; Figure 28–23 & Tabin, C.J. (2006) The calmodulin pathway and evolution of elongated beak Adapted from Szyman´ski, M. & Barciszewski, J. (2002) Beyond the proteome: morphology in Darwin’s fi nches. Nature 442, 565, Fig. 4. non-coding regulatory RNAs. Genome Biol. 3, 6; Figure 28–24 Adapted from BMInd.indd Page I-1 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index

Key: b ϭ boxed material; f ϭ fi gures; s ϭ structural acetyl-CoA–ACP transacetylase, 837f actin, 8, 8f, 181–183, 183f formulas; t ϭ tables; boldface ϭ boldfaced terms acetyl-CoA carboxylase in ATP hydrolysis, 181, 182, 183, 183f in text in bacteria, 840–841 in muscle contraction, 182–183, 183f in fatty acid synthesis, 833, 834f, 835f, structure of, 181–182 840–841, 842f in thin fi laments, 182–183, 183f A in plants, 841 actin-myosin complex A bands, 181, 181f acetyl-coenzyme A. See acetyl-CoA ATP in, 525–526 A (aminoacyl) binding site, ribosomal, 1128 acetyl groups phosphorylation of, 487–488 A-DNA, 291, 291f in fatty acid synthesis, 840, 841f actin-myosin interactions, 182–183, 183f A kinase anchoring proteins (AKAPs), 447 transport of, 840, 841f -actinin, 181 AAAϩ ATPase, 1019–1020 acetylation, enzyme, 229 actinomycin D, 1068, 1069f abasic site, in base-excision repair, acetylcholine, 468s action spectrum, 774, 774f 1030–1031, 1032f acetylcholine receptor, 424 activated acetate. See acetyl-CoA ABC excinuclease, 1032 defective, 426t activation barrier, 27, 27f ABC transporter, 413, 414f open/closed conformation of, 468, 469f activation energy, 27, 27f, 193 ABCA1 protein, 874 in signaling, 467–468, 469f of enzymatic reactions, 193 abiotic synthesis, 33–34, 33f structure of, 467–468, 469f in membrane transport, 403–404, 404f absolute confi guration, 78 synaptic aggregation of, 398 rate constant and, 194 absolute temperature, units of, 507t acetylene, 529s activators, 1157, 1158f absorbance (A), 80b N-acetylgalactosamine, in glycosaminoglycans, active site, 158, 192, 192f absorption 260, 261f active transport, 405, 409 of fat, in small intestine, 668–669 N-acetylglucosamine (GlcNAc), 249f, 250 ATP in, 525–526, 757 of light, 771–776. See also light, absorption of in bacterial cell walls, 259–260 primary, 405, 409 absorption spectra in glycosaminoglycans, 260, 261f secondary, 405, 409 of cytochrome c, 736f in peptidoglycan synthesis, 823–824, 824f transporters in, 404 of nucleotides, 286, 286f N-acetylglutamate, 708 activity, 95 of opsins, 480, 481f N-acetylglutamate synthase, 708 Actos (pioglitazone), 852, 852s, 964–965, 970t ACAT (acyl-CoA–cholesterol acyl transferase), 864 N-acetylmuramic acid (Mur2Ac), 249f acute lymphoblastic leukemia, 895–897 acceptor control, 760 in peptidoglycan synthesis, 823–824, 824f acute pancreatitis, 699 acceptor control ratio, 760 N-acetylneuraminic acid (Neu5Ac), 249s, 250, acyclovir, 1026–1027 accessory pigments, 772f, 773–774, 774f 269–270, 270s, 366s acyl-carnitine/carnitine transporter, 671 acetaldehyde, 529s in gangliosides, 366, 366s acyl carrier protein (ACP), 836, 836f, 837f acetals, 245–246, 245f acetylsalicylate, 845–846 acyl-CoA, fatty, 670–671 acetate, 521s acetylsalicylic acid, 846s conversion of fatty acids into, 670–671, 671f activated. See acetyl-CoA achiral molecules, 17f acyl-CoA acetyltransferase, 674 in citric acid cycle, 637f acid(s). See also specifi c acids, e.g., acetic acid acyl-CoA–cholesterol acyl transferase (ACAT), 864 in cholesterol synthesis, 859–860, 860f amino acids as, 84–85 acyl-CoA dehydrogenase, 674, 740 in fatty acid synthesis, 840, 841f as buffers, 63–69, 65f medium-chain, 682 oxidation of, 649–651 defi nition of, 61 acyl-CoA synthetases, 670, 849–850 as source of phosphoenolpyruvate, 656–657 dissociation constant (Ka) of, 61f–63f, in triacylglycerol synthesis, 848f, 849–850 transport of, 840, 841f 62–63 acyl-enzyme intermediate, in chymotrypsin acetic acid, 521s, 529s fatty. See fatty acid(s) mechanism, 214–218, 215f, 216f, 217

pKa of, 83–84, 84f relative strength of. See pKa acyl phosphate, 552 titration curve for, 62, 62f strong, 61–62 N-acylsphinganine, 857, 895f acetic acid–acetate buffer system, 64, 64f titration curve for, 62–63, 62f, 63f N-acylsphingosine, 857, 859f acetoacetate, 686, 959s Henderson-Hasselbalch equation for, adaptor hypothesis, 1104, 1104f acetoacetate decarboxylase, 686 64–65, 84 adaptor proteins, in signaling, 446, 460–464 acetoacetyl-ACP, 837f, 838 weak, 61–63 ADARs, 1112–1113 acetoacetyl-CoA, 307 acid anhydride, standard free-energy adenine, 10s, 282, 282t, 533s. See also purine acetone, 529s, 686, 959s changes of, 509t bases in diabetic ketoacidosis, 959 acid-base catalysis deamination of, 299, 300f N-acetyl--D-glucosamine, 249s general, 199, 199f evolutionary signifi cance of, 1093 acetyl-CoA, 14s specifi c, 199 adenine nucleotide(s) amino acid degradation to, 717–719, 718f, 719f acid-base pairs, conjugate, 61, 61f biosynthesis of, regulatory mechanisms in, AMPK and, 963 as buffer systems, 63–69 914–915, 915f oxidation yielding, 673f acid-base titration, 62–63, 62f, 63f, 83–84, 83f cellular, 518t in cholesterol synthesis, 860–864, 860f acid dissociation constant (Ka), 61f–63f, 62–63 in metabolic regulation, 594–595 decarboxylation of pyruvate to, 636–637, 637f acidemia adenine nucleotide translocase, 757 in fatty acid synthesis, 833–834, 834f, 835f, argininosuccinic, 717t adenosine, 283s 838–839, 951–953 methylmalonic, 717t, 724b–725b anti form of, 290, 290f in glucose metabolism, 951–952, 952f, acidic activation domain, 1181 as enzyme cofactor, 306–308, 307f 957f, 958 acidic sugars, 249s evolutionary signifi cance of, 307–308 hepatic metabolism of, 942 acidosis, 61, 67–68, 68b, 688 methylation of, 302 hydrolysis of, 521, 521s, 521t diabetic, 67, 688, 960 syn form of, 290, 290f oxidation of, in citric acid cycle, 675–677, 676t acivicin, 923, 952 adenosine 2Ј,3Ј-cyclic monophosphate, 284s oxidation of pyruvate to, 634, 634f aconitase, 641, 642b–643b, 642f adenosine 3Ј,5Ј-cyclic monophosphate. See cAMP oxidation yielding, 674–675 cis-aconitate, 641, 641s (adenosine 3Ј,5Ј-cyclic monophosphate) in plant gluconeogenesis, 825–826 isocitrate formation via, 641, 641f adenosine 2Ј-monophosphate, 284s production of, 840 aconitate hydratase, 641 adenosine 3Ј-monophosphate, 284s in citric acid cycle, 633–638, 634f–637f, 650f ACP (acyl carrier protein), 837f adenosine 5Ј-monophosphate, 284s. See also AMP by pyruvate dehydrogenase complex, acquired immunodefi ciency syndrome (AIDS), (adenosine monophosphate) 654–655, 654f 218–219, 1088, 1089b adenosine deaminase, 920 acetyl-CoA acetyl transferase, 860 acridine, 1068, 1069f adenosine deaminase defi ciency, 922 I-1 BMInd.indd Page I-2 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-2 Index

adenosine diphosphate (ADP). See ADP alanine, 10s, 79, 79s, 696, 715, 895 in glucose transporter, 405f (adenosine diphosphate) degradation of to pyruvate, 715, 715f in keratin, 126, 126f adenosine monophosphate (AMP). See AMP properties of, 77t, 79 in membrane proteins, 391, 392 (adenosine monophosphate) stereoisomers of, 76–77, 76f in myoglobin, 132, 133 adenosine phosphoribosyltransferase, 922 in transport of ammonia to liver, 703 in polysaccharides, 258–259, 260f adenosine triphosphate (ATP). See ATP (adenosine alanine aminotransferase (ALT), 703 in protein folding, 137–138, 151b triphosphate) measurement of, 708b protein folding and, 137 S-adenosylhomocysteine, 712 alanylglutamylglycyllysine, 86s right- vs. left-handed, 120, 121b S-adenosylmethionine (adoMet), 712, 712s Alberts, Alfred, 873b in small globular proteins, 133t as mutagen, 301f, 302 albinism, 717t oxidation, 685–686. See also oxidation synthesis of, 714f albumin, serum, 669, 943 in endoplasmic reticulum, 685f adenylate, 282t, 283s alcohol(s), 529s in peroxisomes, 685–686, 685f adenylate kinase, 526, 594, 916 fermentation of, 544, 548f, 565, 565f ALT. See alanine aminotransferase (ALT) adenylyl cyclase, 438 hemiacetals and, 245, 247f Altman, Sidney, 1083 activation of, 439f, 446 hemiketals and, 245, 247f altrose, 246s adenylyl group, ATP and, 524 in lipid extraction, 377–378, 377f Alzheimer disease adenylylation, 229f, 524 alcohol dehydrogenase, 534t, 565, 685 amyloid deposits in, 150, 349 adenylyltransferase, 889 reaction mechanism of, 565f apolipoprotein in, 866b adhesion receptors, in signaling, 436f, 437 aldehyde(s), 12 linkage analysis for, 347–349, 348f adipocytes, 360–361, 360f, 943, 943f hemiacetals and, 245, 247f protein misfolding in, 150 NADPH synthesis in, 839, 840f hemiketals and, 245, 247f -amanitin, 1068 adipokines, 960 aldehyde dehydrogenase, 685 Amaryl (glyburide), 970t adiponectin, 964–965, 965f aldohexoses, 245, 246f Ames, Bruce, 1027 adipose tissue aldol condensation, 513 Ames test, 1027–1028, 1028f brown, 762–763, 944, 945f aldolase, 593t, 809 amide, standard free-energy changes of, 509t heat generated by, in oxidative in Calvin cycle, 805 amines, 12 phosphorylation regulation, 762–763, 763f aldolase reaction mechanism, class I, 551f as products of amino acid decarboxylation, mitochondria in, 762–763 aldonic acids, 250 908–909, 910f endocrine functions of, 936f, 943–944 aldopentoses, 244 amino acid(s), 8f, 76–85. See also protein(s); in fasting/starvation, 957f, 958f structure of, 244f, 248f, 249f specifi c amino acids fatty acid release from, 849–850, 851f, 943–944 aldoses, 244, 244f abbreviations for, 77t fatty acid synthesis in, 943–944. See also fatty D isomers of, 245 acid-base properties of, 84–85 acid synthesis L isomers of, 245, 246f activation of, in protein synthesis, 1119–1123, glucagon and, 956, 956t structure of, 245, 246f 1120f–1122f glyceroneogenesis in, 850–852, 851f aldosterone, 372, 372s addition of, in protein synthesis. See protein leptin synthesis in, 961, 961f algae, cell walls of, heteropolysaccharides in, synthesis metabolic functions of, 936f, 943–944 259–260, 260f in helix, 121–122, 122f, 122t triacylglycerol mobilization in, 668f, 670f alkaline phosphatase, 315t ammonium assimilation into, 888–889 triacylglycerol recycling in, 850, 850f alkalosis, 61, 68b as ampholytes, 81 white, 943, 943f alkaptonuria, 717t, 721 aromatic, as precursors of plant substances, Adler, Julius, 473, 473f AlkB protein, in DNA repair, 1033, 1035f 908, 909f adoMet. See S-adenosylmethionine alkene, 529s in bacteria, 907 ADP (adenosine diphosphate) alkylating agents, as mutagens, 301f, 302 in sheet, 123, 123f, 124f, 125f

ATP stabilized relative to, on F1 component, 751f all protein structure, 138, 139f in turns, 123, 124f in fatty acid synthesis, 837f, 838 all protein structure, 138, 139f biosynthesis of, 891–902, 891f phosphoryl transfer to all-trans-retinal, 477 allosteric regulation of, 899–902, 904f from 1,3-bisphosphoglycerate, 552–554 allantoin, 921 chorismate in, 897–898, 900f–903f from phosphoenolpyruvate, 554–555 alleles, 172 glutamine amidotransferases in, in photosynthesis, 809 alligator, movement of, 564b 890–891, 890f synthesis of, 26 allopurinol, 923 histidine in, 898–899, 903f ADP-glucose, 819 xanthine oxidase inhibition by, 923, 923f interlocking regulatory mechanisms in, in glycogen synthesis, 818–819 allose, 246s 899–902, 904f in starch synthesis, 818–819 allosteric effectors, 226 -ketoglutarate in, 891f, 892, 893f, 894f ADP-glucose pyrophosphorylase, in starch allosteric enzymes, 226–228, 227f, 228f metabolic precursors in, 892, 892t synthesis, 821, 821f conformational changes in, 226–227, 227f oxaloacetate and pyruvate in, 895–898 ADP-ribosylation, enzyme, 229, 229f kinetics of, 227–228, 228f 3-phosphoglycerate in, 892–894, adrenal, 936f allosteric modulators, 226 894f, 895f adrenaline. See epinephrine allosteric proteins, 166 branched-chain adrenergic receptors, 438–446 ligand binding of, 166, 166f. See also catabolic pathways for, 674, 675f, 718f, adrenocortical hormones, 933t, 935 protein-ligand interactions 722f, 723f adrenoleukodystrophy, X-linked, 683 allosteric regulation not degraded in liver, 723, 723f Adriamycin (doxorubicin), 993b, 993s of acetyl-CoA production, 654–655, 654f as buffers, 84, 84f adsorption chromatography, 377f, 378 of amino acid biosynthesis, 899–902, 904f carbon designations for, 77–78 adult stem cells, 1192 of aspartate transcarbamoylase, 916, 916f codons for, 1105. See also codons AE (anion exchange) protein, 407 of carbohydrate metabolism, 624–626, 626f conversion of Aequorea victoria, fl uorescent proteins in, lipid metabolic integration with, 626 to -ketoglutarate, 721–722, 721f 448b–449b of fat metabolism, 626 to glucose and ketone bodies, 711, 711f aerobic metabolism, of small vertebrates, 564b of glutamine synthetase, 889 to succinyl-CoA, 722, 722f aerobic organisms, evolution of, 35–36, 36f of glycogen phosphorylase, 621–622, 621f degradation of affi nity, receptor-ligand, 433–434, 434f of phosphofructokinase-1, 604, 604f to acetyl-CoA, 717–719, 718f, 719f affi nity chromatography, 91f, 92, 93t, 325–327 of pyruvate kinase, 606–608, 607f to pyruvate, 715–717, 715f, 717t tags in, 325–327, 325t Alper, Tikvah, 150b discovery of, 76 African sleeping sickness, 211b–212b -amino groups, transfer to -ketoglutarate, electric charge of, 84 agar, 260 699–700, 699f, 701f essential, 709, 709t, 892 agarose, 260, 260f, 262t ϩ protein structure, 138, 139f biosynthesis of, 895–898, 896f, 897f agarose gels, in electrophoresis, 260 / barrel, 138, 138f in expanded genetic code, 1124b–1126b aggrecan, 266 / protein structure, 138, 139f in general acid-base catalysis, 199, 199f aging, mitochondrial DNA damage and, 732, 766 cells, pancreatic, 953, 953f glucogenic, 574, 574t, 711 agonists, receptor, 438 chains, in collagen, 127–130, 127f hepatic metabolism of, 941–942, 941f Agre, Peter, 418, 418f helix, 120–122, 120f, 122f, 123–124, 124f, ketogenic, 711 AIDS, 218–219, 1088, 1089b 125f, 126t light absorption by, 80b, 80f AKAPs (A kinase anchoring proteins), 447 amino acids in, 121–122, 122t molecular weight of, 87 BMInd.indd Page I-3 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-3

molecules derived from, 902–910 peptide cleavage in, 99–100, 99f, 100t anemia nonessential, 709t, 892 reagents for, 98–100, 98f–100f, 98s megaloblastic, 714 biosynthesis of, 895 steps in, 98f pernicious, 681, 713 number of, 87t, 88, 88t amino acid substitutions, 106 aneuploidy, 1045b in peptide synthesis, 102–104, 103f in homologs, 106, 107f Anfi nsen, Christian, 144

pKa of, 83–84, 83f–85f amino groups, transfer to -ketoglutarate, angina pectoris, 460 in plant gluconeogenesis, 825–826 699–700, 699f, 701f angstrom (Å), 120 polarity of, 79 amino sugars, 249s anion-exchange (AE) protein, 407–409 polymers of. See peptide(s); protein(s) amino-terminal residues, 86 anion exchanger, in ion-exchange chromatography, as precursors of creatine and glutathione, protein half-life and, 1147, 1148t 90, 91f, 93t 906–907, 908f aminoacyl (A) binding site, ribosomal, 1128 ankyrin, 398f R groups of, 76, 77t, 78–81 aminoacyl-tRNA, 1104 annealing, of DNA, 297–298, 297f relative amounts of, 88, 88t binding of, 1130, 1131f annotated genome, 38 stereoisomerism in, 76f, 97–77 sites of, 1128, 1128f annular lipids, 391, 392f structure of, 76–78, 76f, 83f formation of, 1119–1123, 1120f–1122f anomeric carbon, 246 symbols for, 77t aminoacyl-tRNA synthetases, 1104 anomers, 246 titration curves of, 83–84, 83f, 85f in protein synthesis, 1119–1123, anorexigenic neurons, 962 uncommon, 81 1120f–1122f antagonists, receptor, 438 zwitterionic form of, 81, 83, 83f reaction mechanism of, 1120f antenna chlorophylls, in light-driven electron amino acid arm, of tRNA, 1118 -aminobutyric acid (GABA), 909 fl ow, 778, 781–782, 781f amino acid catabolism, 695–704. See also amino receptor for, as ion channel, 424 antenna molecules, 774 acid oxidation aminolevulinate, biosynthesis of, 905f antennapedia, 1191 acetyl-CoA in, 717–719, 718f, 719f aminopeptidase, 699 anterior pituitary, 936f, 937 ammonia in, 703–704 aminopterin, 925 antibiotics alanine transport of, 703, 703f aminotransferase, 699 mechanism of action of, 224, 418, 418f, 925, glutamate release of, 700–702, 703f prosthetic group of, 699, 718f 992b–993b glutamine transport of, 702–703, 703f ammonia protein glycosylation inhibition by, 1141–1142 asparagine in, 724, 724f in amino acid catabolism quinolone/fl uoroquinolone, 992b–993b aspartate in, 724, 724f alanine transport of, 703, 703f resistance to enzyme cofactors in, 712–715, 712f–714f glutamate release of, 700–702, 702f ABC transporters and, 413 enzyme degradation of protein in, glutamine transport of, 702–703, 702f plasmids in, 981 696–699, 715f from amino acid metabolism, 941 topoisomerase inhibitor, 992b–993b genetic defects in, 717t, 718–721, 720f in nitrogen metabolism, 888–889 transcription inhibition by, 1068 glucose and ketone bodies in, 711, 711f reduction of nitrogen to, 882–883 translation inhibition by, 1138–1139 -ketoglutarate in, 721–722, 721f solubility in water, 51, 51t antibodies, 174. See also immunoglobulin(s) overview of, 696, 697f, 710–711, 711f toxicity of, 703–704 in analytic techniques, 178–179, 179f oxaloacetate in, 724, 724f urea production by, enzymatic steps in, antigens and, 175, 176f, 177f. See also pathways of, 695, 710–725, 719f, 942t 704–706, 705f, 706f antigen-antibody interactions pyruvate in, 715–717, 715f, 717t ammonium cyanide, adenine synthesis from, 1093 binding sites on, 175–177, 176f succinyl-CoA in, 722, 722f ammonotelic species, 704 binding specifi city of, 175, 177–178, 177f transfer of -amino groups to -ketoglutarate in, amoxicillin, 224 diversity of, 175 699f, 701f, 722 AMP (adenosine monophosphate) recombination and, 1049–1051 amino acid metabolism, 588f, 942t allosteric enzyme modifi cation by, 235 monoclonal, 178 amino acid oxidation, 696–704. See also amino acid concentration of, 594 polyclonal, 178 catabolism relative changes in, 594t anticodon(s), 1109–1110, 1110f fates of amino groups in, 696–704 variant forms of, 284, 284s wobble base of, 1110 nitrogen excretion and urea cycle in, AMP-activated protein kinase (AMPK), 594, 595f anticodon arm, of tRNA, 1118 704–710 adiponectin and, 964–965, 965f antidiuretic hormone (ADH), 938f pathways of degradation in, 710–725 in regulating ATP metabolism, 964, 964f antigen(s), 175 amino acid residues, 76, 81, 81s leptin and, 963 epitope of, 175 amino-terminal, 86 amphibolic pathway, 650 T-cell binding of, 175 carboxyl-terminal, 86 amphipathic compounds, 50t, 52 antigen-antibody interactions, 174–179, 176f, 177f carboxylation of, 1136, 1137f solubility in water, 50t, 52–53 binding affi nity in, 177–178, 177f in consensus sequences, 230–231, 231t amphitropic proteins, 390 binding sites for, 175–177, 176f farnesylation of, 1136, 1137f ampholytes, amino acids as, 81 conformational changes in, 177, 177f isoprenylation of, 1137, 1137f amphoteric substances, amino acids as, 81 haptens in, 175 methylation of, 1136, 1137f amplifi cation, signal, 434, 434f, 443–444 induced fi t in, 157, 177, 177f number of, 87, 87t, 88t amylase, 257, 558–559 specifi city of, 175, 177–178 phosphorylation of, 229–231, 229f amylo (1n4) to (1n6) transglycosylase, 619, 619f strength of, 177–178 amino acid sequences, 31, 31f, 96–108, amyloid, 148 antigenic determinant, 175 96f, 97f amyloid deposits, in Alzheimer disease, 150, 349 antigenic variation, 1174t helix and, 120–122, 122f, 123–124 amyloidoses, 148–151 antiporter(s), 409, 409f determination of, 97–102. See also amino acid amylopectin, 255, 256f, 262t, 819. See also starch NaϩKϩ ATPase, 411–412, 412f, 417 sequencing amyloplast, 800–801, 800f, 801f in membrane polarization, 464f evolutionary signifi cance of, 104–108 amylose, 255, 256f, 262t. See also starch in retina, 477 in genetic code, 1105–1106. See also codons structure of, 256f, 258–259, 258f, 259f, 260f for triose phosphates, 780f, 809–810 homologous, 106–107, 106f, 107f anabolic pathways, 799, 942t antiretroviral agents, 218–219 hydrophobicity of, 391–392 energy carriers in, 503f antithrombin III, 234 membrane protein topology and, 390f, 391 in glycogen metabolism, 613–614 AP endonucleases, 1031 nucleic acid sequences and, 980, 980f anabolism, 28, 28f, 502–503, 503f AP site, in base-excision repair, 1030, 1031, 1032f protein function and, 97 citric acid cycle in, 650, 651f Apaf-1, 764 protein structure and, 104 anaerobic bacteria, 884b–885b APC mutation, 492, 492f signature, 107, 107f incomplete citric acid cycle in, 650, 650f apoaconitase, 643b amino acid sequencing, 97–102 anaerobic metabolism, of coelacanths, 564b apoB-48, gene for, RNA editing in, 1112–1113 bond cleavage in, 98–100, 99f, 100t analytes, 100 apoB-100, 865f, 866, 868 computerized, 106–107 anammox, 882, 882f, 884b–885b gene for, RNA editing in, 1112–1113 Edman degradation in, 98–100, 98f anammoxosome, 885b APOBEC enzymes, 1112 in evolutionary analysis, 104–108, 106f–108f anaplerotic reaction, in citric acid cycle apoE, in Alzheimer disease, 865, 866b historical perspective on, 97–98 intermediates, 650–651, 651f, 651t apoenzyme, 190 for homologs, 106–107, 106f, 107f Andersen disease, 617t apolipoproteins, 669, 864–865, 865f, 866t for large polypeptides, 99–100 androgens, 935 in Alzheimer disease, 866b mass spectrometry in, 100–102, 101f, 102f synthesis of, 874, 874f gene for, RNA editing in, 1112–1113 BMInd.indd Page I-4 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-4 Index

apoprotein, 190 association constant (Ka), 160 O2 consumption and, nonintegral stoichiometries apoptosis, 492–494, 494f, 764 in Scatchard analysis, 435b of, 755–757 mitochondria in, 764–765, 764f Astbury, William, 120 by photophosphorylation, 786–788, 787f, 788f apoptosis protease activating factor-1 asymmetry, molecular, 17, 17f proton gradient in, 748–749, 750f, 751–752, 751f (Apaf-1), 764 ATCase, 226–227 proton-motive force and active transport in, apoptosome, 764 atherosclerosis, 871–874, 872b–873b 757, 757f appetite, hormonal control of, 960–968 trans fatty acids and, 361 rotational catalysis in, 752–755 App(NH)p (,-imidoadenosine 5Ј-triphosphate), atom(s) stabilization of, 750–751, 751f 752s electronegativity of, 216 standard free-energy change for, 750–751 aptamers, 1095b hydrogen, electron transfer and, 530 stoichiometry of, 649t aquaporins (AQPs), 418–420, 419t atomic mass unit, 14b ATPase(s) classifi cation of, 419t ATP (adenosine triphosphate), 24s AAAϩ, 1019–1020 distribution of, 419t in active transport, 525–526 F-type, 413–414, 413f. See also ATP synthase(s) permeability of, 419t in ATCase synthesis, 227, 227f in membrane transport, 410–413, 411f–413f, aqueous environments, adaptation to, 69–70 oxidation yielding, 674–675, 676t 417, 417f aqueous solutions. See also water in Calvin cycle, 808–809, 808f–811f NaϩKϩ, 411–412, 412f, 417, 417f amphipathic compounds in, 50t, 52–53 cAMP synthesis from, 438, 439f, 440f in membrane polarization, 464, 464f buffered, 63–69, 65f concentration of, 594 in membrane transport, in neurons, 949 colligative properties of, 55, 56f energy by group transfer and, 522–523, in retina, 477 hydrophilic compounds in, 50–52, 51f 522f, 523f P-type, 410–411 hydrophobic compounds in, 9, 50, 50–53, in glycolysis, 544–558 V-type, 413 51f, 52f balance sheet for, 555 atrial natriuretic factor (ANF), 459 hypertonic, 56–57, 56f in payoff phase, 550–555, 553f, 554f attractants, 473 hypotonic, 56–57, 56f in preparatory phase, 548–550, 551f, 552f autocrine hormones, 933 ionic interactions in, 50 in heart muscle, 948 Autographa californica, recombinant gene isotonic, 56–57, 56f hydrolysis of. See ATP hydrolysis expression in, 323 osmolarity of, 56–57, 56f in hypoxia, 760 autonomously replicating sequences (ARSs), 1025 pH of, 59–61, 60f, 60t inhibition of pyruvate kinase by, 607f autophagy, 149 weak acids/bases in, 61–63 magnesium complexes of, 518, 518f autophosphorylation, 453–454. See also weak interactions in, 47–58. in metabolism, 26, 28f phosphorylation Arabidopsis thaliana in muscle contraction, 525–526, 944–948, 948f of insulin-receptor tyrosine kinase, 454, 454f aquaporins in, 418–419 in nitrogen fi xation, 886–887, 888 in receptor enzyme activation, 454, 454f cellulose synthesis in, 822, 822f nucleophilic displacement reaction of, in signaling, 454 signaling in, 474, 474t, 475–476 523–524, 524f in bacteria, 473, 473f arabinose, 246s phosphoryl group transfers and, 517–519 in plants, 475f, 476 arachidic acid, 358t in photosynthesis, 808–812 autotrophs, 4, 5f, 501 arachidonate, 468f, 842f, 845 synthesis of, 808–809, 809, 811f auxins, 475s, 908 arachidonic acid, 358t, 371, 371s transport of, 780f, 809–810 Avandia (rosiglitazone), 852, 852s, 964–965, 970t Arber, Werner, 314 in proteolysis, 1146f Avery, Oswald T., 288 archaea, 4, 4f, 5–6, 6f and regulation of oxidative phosphorylation, Avery-MacLeod-McCarty experiment, 288 membrane lipids of, 365–366, 366f 759–762, 761f, 762f avian sarcoma virus, 1088, 1088f architectural regulators, 1158 relative changes in, 594t avidin, 653 arginase, 706 in replication initiation, 1019–1020, 1020f Avogadro’s number (N), 507t arginine, 79s, 81, 721–722, 892 supply of, 594 azaserine, 923, 923f biosynthesis of, 892, 893f synthesis. See ATP synthesis Azotobacter vinelandii, nitrogen fi xation by, conversion of, to -ketoglutarate, 721–722, 721f yield of, from oxidation of glucose, 760t 883, 887 in nitric oxide biosynthesis, 909, 911f ATP-binding casette (ABC) transporter, AZT, 1089b properties of, 77t, 81 413, 414f argininemia, 717t ATP-gated Kϩ channels, 954 argininosuccinate, 706 ATP hydrolysis, 306, 306f B argininosuccinate synthetase, 706 actin in, 182, 183, 183f B cells (lymphocytes), 175 reaction mechanism of, 706f equilibrium constant for, 511 B-DNA, 291, 291f argininosuccinic acidemia, 717t free-energy change for, 517–519, 518f, 520f bacmids, 323, 324f Arnon, Daniel, 786, 786f chemical basis for, 518f BACs (bacterial artifi cial chromosomes), 319, 320f aromatic amino acids. See also amino acid(s) free energy of, within cells, 519 bacteria, 4–6, 5f. See also Escherichia coli as precursors of plant substances, 908, 909f in ischemia, inhibitory proteins in, 760, 760f amino acids in, 907 -arrestin (arr), 445f, 446 in membrane transport, 410–414, 411f, 412f anaerobic, 884b–885b arrestin 1, 480 in muscle contraction, 182, 183, 183f, 944–948 incomplete citric acid cycle in, 650, 650f arrestin 2, 445f, 446, 446 myosin in, 182, 183, 183f anammox, 882, 882f, 884b–885b artifi cial chromosomes, 321f, 985 as two-step process, 522–523, 522f antibiotic-resistant, 224, 225f bacterial, 319 ATP-producing pathways, regulation of, ABC transporters and, 413–414 human, 985 761–762, 762f plasmids in, 981 yeast, 320, 321f, 985 ATP synthase(s), 747 cell structure of, 4–6, 6f artifi cial sweeteners, 255b subunits of, conformations of, 752 cell walls of ascorbate, 129s binding-change model for, 754f heteropolysaccharides in, 259–260 ascorbic acid. See vitamin C (ascorbic acid) of chloroplasts, 787–788, 788f synthesis of, 824f asparaginase, 724 functional domains of, 750 cellulose synthesis in, 823 asparagine, 79s, 81, 724, 895 in membrane transport, 413 DNA replication in, 1011–1025 degradation of, to oxaloacetate, 724, 724f ATP synthasome, 757 endosymbiotic, 36, 37f properties of, 77t, 81 ATP synthesis, 747–759 chloroplasts evolved from, 788–789 aspartame, 87s, 255b ATP synthase in in eukaryotic evolution, 36, 37f stereoisomers of, 20f, 255b conformations of subunits of, 752 mitochondria evolved from, 765–766, 790f aspartate, 10s, 79s, 81, 696, 724, 895 functional domains of, 750 evolution of, 35–36, 36f, 788–790

in C4 pathway, 815f, 816 binding-change mechanism for, rotational fatty acid synthesis in, 834–839, 843 degradation of, to oxaloacetate, 724, 724f catalysis in, 752–755, 754f gene regulation in, 1165–1174 properties of, 77t, 81 chemiosmotic theory of, 731, 747, genes in, 984 pyrimidine nucleotide synthesis from, 747–749, 748f genetic map of, 1010f 915–916, 915f coupling of electron transfer and, 748, 749f glycogen synthesis in, 819 aspartate aminotransferase, 708, 708b cytosolic NADH oxidation in, shuttle systems in, gram-negative, 5, 6f aspartate-argininosuccinate shunt, 707 758–759, 758f, 759f gram-positive, 5, 6f aspartate transcarbamoylase, 226–227, 227f, 915 equation for, 747 green sulfur, photochemical reaction center in, aspirin, 234, 845–846, 846s in halophilic bacteria, 789–790 776, 777f BMInd.indd Page I-5 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-5

gut, obesity and, 968 base stacking, 286 biochemical reactions halophilic, in ATP synthesis, 789–790, 791f in DNA, 288–289, 289f bond cleavage in, 512–513 lectins and, 271–272, 271f, 273f in replication, 1013, 1014f common types of, 511–517 lipopolysaccharides of, 268, 268f in RNA, 286, 294–295 electrophilic, 512, 512f lithotropic, 884b basic helix-loop-helix, 1163, 1164f eliminations in, 513–514 nitrifying, 884b–885b Beadle, George W., 642b, 979, 980f free-radical, 514–515 nitrogen-fi xing, symbiotic relationship with beads-on-a-string formation, 995, 996f group transfer, 515–516, 515f leguminous plants, 887–888, 887f beer brewing, fermentation in, 565, 566b internal rearrangements in, 513–514 nucleoids in, 1002, 1003f Beery, Alexis, 340b isomerization in, 513–514 peptidoglycan synthesis in, 823–824, 824f Beery, Joe, 340b nucleophilic, 512, 512f potassium channel in, 422–424, 422f, 436f Beery, Noah, 340b oxidation-reduction. See oxidation-reduction purple Beery, Retta, 340b reactions bacteriorhodopsin in, 391, 391f beeswax, 362, 362f vs. chemical reactions, 517 reaction centers in, 776–777, 777f, 778f benzoate, 710s biochemical standard free-energy change reaction centers in, 776–778, 777f, 778f for hyperammonemia, 709 (⌬GЈº), 192, 193f recombinant gene expression in, 322, 322f benzoyl-CoA, 709, 710s biochemistry, fundamental principles of, 2 signaling in, 473, 473f, 474t Berg, Paul, 313, 313f bioenergetics, 24–25, 506–507. See also energy structure of, 4–6, 6f Bergström, Sune, 371, 371f oxidation-reduction reactions and, 528–537 in waste treatment, 884b–885b Berson, Solomon, 930 phosphorylation and, 517–519 bacterial artifi cial chromosomes (BACs), 319, 320f Best, Charles, 931b thermodynamics and, 506–507 bacterial DNA, 981, 982t -- loop, 137, 137f, 138f biofuels, from fermentation, 566b packaging of, 1002–1003, 1003f -adrenergic receptor, 438–446 bioinformatics, 104–105 topoisomerases and, 990 in rafts, 463 biological energy transformation, in bacterial genes, 984 structure of, 438, 439f thermodynamics, 506–507, 507t mapping of, 1010f -adrenergic receptor kinase (ARK), biological waxes, 362, 362f naming conventions for, 1010 444–445, 445f bioluminescence cycle, of fi refl y, 525b bacterial genome, 981, 982t adrenergic response, in signaling, termination of, biomass bacterial ribosome, 1115–1117, 1116f 444–445 ethanol from, 816b–817b bacteriophage lambda vector, 315t, 317 -adrenergic signaling pathway, 438–446, 439f, photosynthetic, 257 bacteriorhodopsin, 391, 790 440f, 444f, 445f biomolecules, 1. See also under molecular light-driven proton pumping by, 790, 791f barrel, 137f, 393–394, 393f amphipathic, 50t in purple bacteria, 391 in membrane proteins, 393–394 asymmetric, 17, 17f structure of, 391, 391f in membrane transport, 393f average behavior of, 30 baculoviruses, recombinant gene expression in, cells, 175t chirality of, 17, 17f 323, 324f pancreatic, 953–955, 953f conformation of, 19, 19f Bainbridge, Matthew, 340b recombination in, 1049–1051, 1052f derived from amino acids, 902–910 ball-and-stick model, 16, 16f conformation, 123–125, 123f, 124f functional groups of, 12–14, 13f, 14f Ballard, John, 850 in small globular proteins, 133t interactions between, 9–10 Baltimore, David, 1087, 1087f structural correlates of, 126t light absorption by, 80b, 80f Banting, Frederick G., 931b conformation sheet. See sheet macromolecules, 15 BAR domains, 400, 401f oxidation, 667. See also oxidation molecular mass of, 14b basal transcription factors, 1178 in bears, 676b molecular weight of, 14b base(s) enzymes of, 683–684, 684f nonpolar, 50, 50t amino acids as, 74–75 in peroxisomes, 663f, 682–683 origin of, 33–34, 33f. See also evolution in buffer systems, 63–69, 66f in plants, 683, 684f polar, 49–50, 50t nucleotide/nucleic acid, 281–287, 282f–284f, steps in, 673–675, 673f, 675f size of, 9 282s–284s, 282t, 283s, 284s yielding acetyl-CoA and ATP, 673f, 674–675 small, 14–15 alkylated, repair of, 1033, 1035f sheet, 123–125, 123f, 124f stereospecifi city of, 16, 19, 19f, 20f anti form of, 290, 290f in large globular proteins, 137–138, 138f in supramolecular complexes, 31 Chargaff’s rules for, 288 in protein folding, 137–138, 138f, 151b bioorganisms chemical properties of, 286–287 structural correlates of, 126t classifi cation of, 3–4, 5f, 6f in codons, 1105–1106. See also codons twisted, 137–138, 138f distinguishing features of, 1–2, 2f deamination of, 299–300, 300f sliding clamp, 1017, 1017f, 1022–1023, 1022f biosignaling. See signaling in DNA, 286–287, 287f, 288–289, 289f, 290f subunits, of ATP synthase, different biotin, 570, 651 estimation of via denaturation, 297–298, 297f conformations of, 752 defi ciency of, 653 functional groups of, 286–287 turn, 123, 125f, 126t in phosphoenolpyruvate synthesis from in genetic code, 1105–1106. See also ARK, 445–446, 445f pyruvate, 570, 571f genetic code arr, 445f, 446 in pyruvate carboxylase reaction, 570, 571f, hydrogen bonds of, 286–287, 287f, 288–289, bicarbonate 651–653, 652f, 653f 289f, 290f, 295, 296f as buffer, 61f, 63–69 Bishop, Michael, 1088 methylation of, 302 formation of, 169–170 1,3-bisphosphoglycerate (BPG), 520s, 551 minor, 284, 284f bicoid, 1188–1190 hydrolysis of, 520, 520f nitrous acid and, 301, 301f biguanides, 970, 970t phosphoryl transfer from, to ADP, 552–554 pairing of. See base pairs/pairing bilayer. See lipid bilayer synthesis of, 805–806, 805f, 808–809 in replication, 1013, 1014f bile acids, 370, 370s, 864 2,3-bisphosphoglycerate (BPG), in in RNA, 286, 294–295, 295, 296f bile pigment, heme as source of, hemoglobin-oxygen binding, 171–172, 173f structure of, 10s, 281–284, 282f–284f, 282t, 904–906, 907f bisulfi tes, as mutagens, 301 286–287 bilirubin, 904 black smokers, 34, 34f syn form of, 290, 290f breakdown products of, 907f Blobel, Günter, 1140, 1140f tautomeric forms of, 286, 296 binary switches, in G protein(s), 438, 440f, Bloch, Konrad, 862, 863f variant forms of, 286, 290–291, 290f 441b–443b blood weak interactions of, 286–287, 287f, 289, 290f binding, cooperativity in, 163–169, 165f, 166f buffering of, 61f, 66–67 wobble, 1110 binding-change model, 754 composition of, 949–950, 950f relative strength of. See pKa binding energy ( GB), 195–197 electrolytes of, 950 weak, 61 enzyme specifi city and, 197–198 glutamine transport of ammonia in, base-excision repair, 1028t, 1030–1031, 1032f binding sites, 157, 166–167. See also 702–703, 702f base pairs/pairing, 287, 287f, 288–290, 289f, 290f specifi c types metabolic functions of, 949–950 in DNA, 288–290, 289f. See also DNA structure antibody, 175–177, 176f normal volume of, 949 in replication, 1013, 1014f, 1015, 1015f characteristics of, 174 pH of, 66–67 in DNA-protein binding, 1161–1162, 1161f binding specifi city transport functions of, 163, 949–950 in RNA, 294–295, 295f, 296f antibody, 175, 177–178, 177f blood clotting, integrins in, 471 wobble in, 1110 enzyme, 197–198 blood groups, sphingolipids in, 368, 368f BMInd.indd Page I-6 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-6 Index

blood plasma, 950, 950f cancer blue fl uorescent protein (BFP), 448b–449b C citric acid cycle mutations in, 656 C–C bond. See carbon-carbon bond blunt ends, 316, 317f DNA repair in, 1037b–1038b C–H bond. See carbon-hydrogen bond boat conformation, 249f glucose catabolism in, 555, 556b–557b C-protein, 182 body mass. See also fat, body integrins in, 471 C cycle, 815 regulation of, 849–850, 960–968 2 mutations in, 489–492, 493f, 656, 1027–1028, C plants, 802 leptin and, 961, 961f–964f 3 1037b–1038b photosynthesis in, 802, 815–818 body mass index, 960 oncogenes and, 489, 493f C metabolism, 815–818 Bohr, Christian, 170 4 retroviruses and, 1088, 1088f C pathway, 815–818 Bohr, Niels, 170 4 selectins and, 270 C4 plants, photosynthesis in, 815–818 Bohr effect, 170 ϩ treatment of Ca2 /calmodulin-dependent protein kinases, boiling point chemotherapeutic agents in, 923–925, 451, 451f of common solvents, 48t ϩ 992b–993b Ca2 channels of water, 47, 48t protein kinases in, 490b–491b defective, diseases caused by, 426t Boltzmann constant (k), 507t targeting enzymes in nucleotide biosynthesis in glucose metabolism, 953f, 954 bond(s). See also weak interactions in, 923–925, 923f, 924f in signaling, 465–466, 466f, 468 carbon, 12–14, 12f, 13f ϩ topoisomerase inhibitors in, 992b–993b Ca2 concentration, in cytosol vs. extracellular carbon-carbon. See carbon-carbon bond tumor suppressor genes and, 489–492, 493f fl uid, 465t carbon-hydrogen, cleavage of, 512–513, 512f Warburg effect in, 555 oscillation of, 451–452, 452f covalent, 9 ϩ CAP. See cAMP receptor protein (CRP) Ca2 ion channel, 420–421, 424 in enzymatic reactions, 195 ϩ cap-binding complex, 1070, 1104f Ca2 pump, 410–411, 411f heterolytic cleavage of, 512, 512f carbaminohemoglobin, 171s cadherins, 402 homolytic cleavage of, 512, 512f formation of, 171 Cairns, John, 1012, 1016 of phosphorus, 515–516, 515f carbamoyl glutamate, 710s calcitonin, synthesis of, 1077 disruption of carbamoyl phosphate, pyrimidine nucleotide calcitonin gene, alternative processing of, in amino acid sequencing, 98, 99f synthesis from, 915–916, 916f 1077, 1077f energy for, 116 carbamoyl phosphate synthetase I, 706 calcitonin-gene-related peptide, synthesis of, glycosidic, 252 activation of, 708, 709f 1077, 1077f phosphorolysis vs. hydrolysis reactions of, defi ciency of, 717t calcitriol, 372s, 373, 933t, 935 613–614 reaction mechanism of, 706f calcium N-glycosyl, 282 carbamoyl phosphate synthetase II, 915 blood levels of, 950 in disaccharide, 252 carbanion, 512, 808f IP and, 447–448, 450f, 462 hydrolysis of, 300, 300f 3 carbocation, 512 in muscle contraction, 183 hydrogen. See hydrogen bonds carbohydrate(s), 243–276 regulation of, 935 noncovalent, 9, 54–55. See also weak analysis of, 274, 275f in vision, 479, 480 interactions chemical synthesis of, 274 calmodulin (CaM), 451, 451t O-glycosidic, 252 classifi cation of, 243 Calvin, Melvin, 800, 800f peptide. See peptide bonds disaccharide, 243, 252–253 Calvin cycle, 800 phosphate, high-energy, 522 dolichols and, 375 ATP in, 808–812, 808f–811f phosphorus-oxygen, 515–516, 515f Fischer projection formulas for, 244, 245f, 1,3-bisphosphoglycerate in, 804, 805f bond dissociation energy, 48 247–248 in C plants, 815–818, 815f bovine F -ATPase, structure of, 760, 760f 4 glycoconjugates of, 243 1 in CAM plants, 818 bovine spongiform encephalopathy, 150b–151b intermediates of, 249f, 250–251 carbon-fi xation reaction in, 801–804, 801f Boyer, Herbert, 313, 313f lectin binding of, 269–273, 270f, 272f 2-carboxyarabinitol 1-phosphate in, 803f, 804 Boyer, Paul, 752, 752f monosaccharide, 243–251. See also glyceraldehyde 3-phosphate synthesis in, 803f, BPG (2,3-bisphosphoglycerate), in monosaccharides 804–805 hemoglobin-oxygen binding, 171–172, 173f nomenclature of, 243, 244, 250 NADPH in, 801f, 804, 808–812, 808f–811f brain oligosaccharide. See oligosaccharide(s) 3-phosphoglycerate in glucose supply for, 956–958, 957f overview of, 243 conversion of, to glyceraldehyde 3-phosphate, metabolism in, 948–949, 949f oxidation of, 251, 252–253 801, 804–805 brain injury, from ammonia, 703 polysaccharide, 243, 254–263. See also synthesis of, 801–804 branch migration, 1040–1041, 1042f polysaccharide(s) rubisco in, 802–804, 802f–804f branched-chain amino acids, catabolic pathways size classes of, 243 stoichiometry of, 808f for, 674, 675f, 718f, 721f, 723f carbohydrate metabolism, 588f. See also glucose triose phosphates in branched-chain -keto acid dehydrogenase metabolism ribulose 1,5-bisphosphate regeneration complex, 723 anabolic, 942t from, 805–806, 806f, 807f Branson, Herman, 120 catabolic, 942t synthesis of, 805f brassinolide, 372, 372s, 475s in cellular respiration, 633, 634f CaM kinases, 451 brassinosteroids, 475, 475s pathways of, 942t CAM plants, 818 BRCA1/2, 1038b in diabetes mellitus, 559f cAMP (adenosine 3Ј,5Ј-cyclic monophosphate), breast cancer, 1038b enzymes of, 592, 593t 284, 308, 308s Briggs, G. E., 202 gene expression in, insulin and, 624 degradation of, by cyclic nucleotide Brown, Michael, 868, 868f, 873b hepatic, 940–941, 941f phosphodiesterase, 439f, 445 brown adipose tissue (BAT), 763, 944, 945f metabolic control analysis of, 598–600, hormonal regulation of, 446–447 heat generated by, and oxidative phosphorylation 598b–599b measurement of, by FRET, 448b–449b regulation, 762–763, 763f pathways of, 942t in protein kinase A activation, 438–439, mitochondria in, 762–763 in plants, 799–812, 825–826, 825f. See also 439f, 440f Buchner, Eduard, 189, 190f, 544, 596 Calvin cycle as second messenger, 308, 439f, 446–447, 446t buffering region, 64 regulation of in -adrenergic pathway, 438–440, buffers, 63–69, 64, 65f allosteric and hormonal, 624–626, 626f 439f, 440f bulges, in RNA, 295, 295f lipid metabolic integration with, 626 structure of, 308s, 439f bungarotoxin, 426 in liver, 624–626, 626f synthesis of, adenylyl cyclase in, 438, 439f trans-⌬ -butenoyl-ACP, 837f, 838 in muscle, 626, 626f 2 cAMP-dependent protein kinase. See protein butyryl-ACP, 837f, 838 xylulose 5-phosphate in, 606 kinase A (PKA) Byetta (exenatide), 970t carbohydrate response element binding protein cAMP receptor protein (CRP), 1061 bypass reactions, in gluconeogenesis (ChREBP), 609, 609f in gene regulation, 1165–1167 fructose 1,6-bisphosphate to fructose carbohydrate synthesis, 568–575, 569f, 799–826. cAMP response element (CRE), 1184 6-phosphate conversion, 570t, 572–573 See also gluconeogenesis cAMP response element binding protein glucose 6-phosphate to glucose conversion, C pathway in, 815–818 (CREB), 446, 610 4 570t, 573 cellulose synthesis and, 822–823, 824f Campto (irinotecan), 992s, 993b pyruvate to phosphoenolpyruvate conversion as, glycolate pathway in, 813–815, 813f camptothecin, 993b 570–572, 570t, 571f, 572f integrated processes in, 825–826, 825f, 826f BMInd.indd Page I-7 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-7

pentose phosphate pathway in, 801, catabolic pathways, 799, 942t growth factors in, 486f, 487 810–812, 825 energy delivery in, 503f replication in. See DNA replication peptidoglycan synthesis and, 823–824, 824f in glycogen metabolism, 613–614 retinoblastoma protein in, 488, 488f photorespiration in, 812–818 catabolism, 28, 28f, 502, 503f stages of, 484, 484f photosynthetic, 799–812. See also amino acid, 695–704, 710–725. See also amino cell death, programmed, 492–494, 494f photosynthesis acid catabolism cell envelope, 5, 6f starch synthesis in, 818–819, 820–821 glucose, in cancerous tissue, 555, 556b–557b cell fractionation, 8, 8f, 57 sucrose synthesis in, 819–821 protein, fat, and carbohydrate, in cellular cell membrane. See membrane(s) carbon respiration, 634f cell wall polysaccharides, synthesis of, 823–824 anomeric, 246 purine nucleotide, 920–921, 921f in bacteria, 824f asymmetric, 17, 17f pyrimidine, 920–921, 922f cellular differentiation, 589 oxidation of, 512f, 516, 516f, 529f catabolite repression, 1165 cellular functions, of proteins, 332 carbon-assimilation reactions, 769, 809, catalase, 682 cellular immune system, 174. See also 810–812, 811f catalysis, 27–28, 28f, 192–200. See also immune system

in C3 plants, 815–818, 815f enzymatic reactions cellular respiration, 633 in C4 plants, 815–818, 815f acid-base stages in, 633, 634f carbon bonds, 12–14, 12f, 13f general, 199, 199f cellulase, 257, 257f carbon-carbon bonds specifi c, 199 cellulose, 256–257, 262t. See also cleavage of, 512–513, 512f covalent, 200 polysaccharide(s) reactions of, 512–513, 520f metal ion, 200, 220, 221f conformations of, 259f carbon dioxide, 529s regulation of, 226–235 function of, 257, 259, 262t climate change and, 816b–817b rotational, 752–755 structure of, 256–257, 257f, 259, 259f, cycling of, 501–502, 502f vs. specifi city, 197 262t, 821, 822f in hemoglobin-oxygen binding, 170–171 catalytic site, 158 synthesis of, 822–823 hemoglobin transport of, 170–171 catalytic triad, 218 tensile strength of, 259 oxidation of glucose to, 532 catecholamines, 933t, 934–935 cellulose synthase, 822 oxidation of isocitrate to, 641–644, 641f as hormones, 930, 933t, 934–935 central dogma, 977, 977f, 1086 oxidation of -ketoglutarate to, 644 as neurotransmitters, 930 centrifugation, differential, 8 oxidation of pyruvate to, 634, 634f catenanes, 1025 centromere, 984, 984f partial pressure of, 66 cation-exchange chromatography, 90–92, 91f, 93t. ceramide, 366, 367f in photosynthesis. See Calvin cycle See also ion-exchange chromatography in cell regulation, 371 solubility in water, 51, 51t caudal, 1188–1190, 1189f cerebrosides, 366, 367f, 368f, 857, 859f carbon dioxide assimilation, 800, 800f, 801–804, caveolae, 399, 400f synthesis of, 857 801f. See also Calvin cycle caveolin, 399, 400f, 463 ceruloplasmin, 269–270 Ј in C3 plants, 815–818, 818 CCA(3 ), 1080 CFTR, 415b, 424 in C4 plants, 815–818, 815f CCAAT-binding transcription factor 1 (CTF1), cGMP (guanosine 3Ј,5Ј-cyclic monophosphate), in CAM plants, 818 proline-rich activation domains of, 1182 283s, 308, 308s, 459–460 carbon fi xation, 800, 800f, 801–806, 801f. See also CDK9, 1068 in signaling, 459–460, 459f Calvin cycle cDNA (complementary DNA), 332, 1087 structure of, 308s

in C4 plants, 815–818 cloning of, 1096b–1097b in vision, 477, 479–480, 480 carbon-fi xation reactions, 769 in hybridization, 299, 300, 1087 cGMP-dependent protein kinase (protein kinase carbon fl ux, anthropogenic, 816b cDNA library, 332, 332f, 1096b–1097b G), 459–460 carbon-hydrogen bond, cleavage of, specialized, 334, 335f cGMP PDE, 460 512–513, 512f CDP (cytidine diphosphate), 852 chair conformation, 249f carbon monoxide, 529s CDP-diacylglycerol, in lipid biosynthesis, 853–855, Changeux, Jean-Pierre, 167 hemoglobin binding of, 159, 162, 167, 853f, 854f channels. See ion channels 168b–169b Cech, Thomas, 1071–1072, 1072f chaperones, 146–147, 146f, 147f, 148f, 1143, 1145f physiological effects of, 168b–169b cell(s), 2–11 chaperonins, 146, 147, 148f carbon monoxide poisoning, 168b–169b bacterial, 4–6, 6f Chargaff, Erwin, 288 carbonic anhydrase, 170 death of. See apoptosis Chargaff’s rules, 288 carbonyl groups, 513, 513f energy needs of, in oxidative phosphorylation charge 2-carboxyarabinitol 1-phosphate, 804s regulation, 760 of amino acids, 84, 85f in Calvin cycle, 803f, 804 fat cells in, 360–361, 360f pH and, 84, 85f carboxybiotinyl-enzyme, 652s free-energy of ATP hydrolysis in, 519 Chase, Martha, 288 -carboxyglutamate, 81, 81s, 234 metabolic transformations in, 511–512 chemical elements carboxyhemoglobin, 168b–169b origin of, 33–34. See also evolution essential, 12f physiological effects of, 168b–169b size of, 3 trace, 12, 12f carboxyl-terminal residues, 86 sources of free energy for, 507 chemical models posttranslational modifi cation of, 1136 structure of, 9–10, 11f ball-and-stick, 16, 16f carboxylation, of amino acid residues, in bacteria, 4–6, 6f space-fi lling, 16, 16f 1136, 1137f in eukaryotes, 6–8, 7f chemical potential energy, of proton-motive carboxylic acids, 12, 529s hierarchical, 9, 11f force, 744 carboxypeptidase A, 698 synthetic, 36 chemical reaction(s), 20–29. See also under carboxypeptidase B, 698 cell-cell interactions/adhesion, 402 reaction cardiac enzymes, 708b cadherins in, 402 activation energy in, 27, 27f cardiac muscle, 948, 948f integrins in, 266, 266f, 402, 470–471, 470f direction of, 22, 25 cardiolipin, 364f, 386 lectins in, 271–272, 272f driving force of, 27–28 synthesis of, 854f, 855 proteoglycans/oligosaccharides in, 264–268, dynamic steady state and, 21 caretaker genes, 492 269–273 endergonic, 23, 25, 28f carnauba wax, 362, 375s selectins in, 402 energy conservation in, 21, 21f carnitine, 671 cell-cell signaling. See signaling energy-coupled, 24–25, 24f carnitine acyltransferase I/II, 671 cell cultures, mammalian, 323 energy sources for, 24 carnitine shuttle, 670 cell cycle enzymatic, 27–28, 28f, 189–237, 192–200. -carotene, 374, 374s, 772s, 773 chromosome changes in, 994, 994f See also catalysis; enzymatic reaction(s); carotenoids, 772f, 773–774, 773f meiosis in, 1041–1046, 1042, 1043f enzyme(s) carriers. See transporter(s) in bacteria, 1039–1041 at equilibrium, 25 Caruthers, Marvin, 304 in eukaryotes, 1041–1043, 1043f equilibrium constant for, 25 carvone, stereoisomers of, 20f recombination in, 1041–1043, 1044f exergonic, 24, 25, 27, 28f casein kinase II, 623 regulation of in citric acid cycle, 655 CASP competition, 146 cyclin-dependent protein kinases in, in conversion of pyruvate to caspases, 764 485f–487f phosphoenolpyruvate, 570–572, in apoptosis, 493–494 cytokines in, 486f, 487 570t, 571f, 572f BMInd.indd Page I-8 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-8 Index

chemical reaction(s) (Continued) receptor-mediated endocytosis of, circular dichroism (CD) spectroscopy, coupled with endergonic reactions, 24–25, 24f 868–869, 868f 124–125, 125f free energy in, 23, 25–26, 192–193, 193f in steroid hormone synthesis, 372, 372s, 874, cis confi guration, of peptide bonds, 123, 124f ground state in, 192 874f, 875f cis-trans isomers, 17 intermediates in, 217 structure of, 368–369, 368f, 869s citrate, 640, 641s mechanisms of, 216, 216f synthesis of, 860–864, 860f–863f asymmetric reaction of, 648b oxidation-reduction, 22 regulation of, 869–871, 870f in fatty acid synthesis, 840, 841, 841f, 842f rate constant for, 194 trans fatty acids and, 361 formation of, in citric acid cycle, 639f, 640, 641f rate equation for, 194 transport of, 864–871, 867f citrate lyase, 840 rate-limiting steps in, 193 reverse, 867f, 869, 873–874, 874f citrate synthase, 640, 641s, 840 reaction intermediates in, 193 cholesterol intermediates reaction mechanism of, 641f sequential, 510–511 fates of, 874–875, 875f structure of, 640f standard free-energy changes of, 507, 508t synthesis of, 874–875, 875f citrate transporter, 840, 841f at pH 7.0 and 25ЊC, 509t cholesterol-lowering drugs, 872b–873b citric acid cycle, 633–656, 633–659 transition state in, 27, 193, 195–197, 217 cholesteryl esters, 864 acetyl-CoA in, 633–638, 635f vs. biochemical reactions, 517 receptor-mediated endocytosis of, 868f activated acetate in, 652f chemical synthesis, 274 transport of, 864–871, 867f as amphibolic pathway, 650 of DNA, 304, 305f chondroitin sulfate, 261, 261s, 264f anaplerotic reaction replenishing, 650–651, phosphoramidite method in, 304, 305f chorismate, in amino acid biosynthesis, 897–898, 651f, 651t chemical uncouplers, of oxidative phosphorylation, 900f–903f citrate formation in, 639f, 640, 641f 749, 749f ChREBP (carbohydrate response element binding components of, 650, 651f chemicals, industrial, from fermentation, 566–568 protein), 609–610, 609f conversion of succinyl-CoA to succinate in,

chemiosmotic coupling, of O2 consumption and chromatids, sister, 994, 1042–1044, 1043f 644–645, 645f ATP synthesis, 755–757 chromatin, 994, 997f energy of oxidations in, 647–649, 649t chemiosmotic theory, 731, 747–749 acetylation/deacetylation of, 1175–1176 in gluconeogenesis, 574, 957–958, 957f of ATP synthesis, 747 assembly of, 997f in glucose metabolism, 941, 941f, 957–958, 957f prediction of, 749, 750f beads-on-a-string appearance of, glyoxylate cycle and, 658–659, 658f, 659f chemistry, prebiotic, 33–34 995f, 996f in hepatic metabolism, 941, 941f, 957–958, 957f chemotaxis, two-component signaling in, 473, 473f chromosomal scaffolds and, 999, 1000f incomplete, in anaerobic bacteria, 650, 650f chemotherapy condensed, 1175 isocitrate formation in, 641, 641f targeting enzymes in nucleotide biosynthesis, euchromatin, 1175 in lipid metabolism, 941f, 943 923–925, 923f, 924f heterochromatin, 1175 oncogenic mutations in, 656 topoisomerase inhibitors in, 992b–993b, 992s, 993s histones and, 994, 995f, 998b–999b, 1175–1176. oxidation of acetate in, 650, 650f chemotrophs, 4, 5f See also histone(s) oxidation of acetyl-CoA in, 675–677, 676t chi, 1040 nucleosomes in, 996f, 997f, 1000f. See also oxidation of isocitrate to -ketoglutarate and

chimpanzee genome, vs. human genome, nucleosomes CO2 in, 641–644, 643f 345–347, 345f remodeling of, 1175–1176, 1176t oxidation of malate to oxaloacetate in, 647 chiral center, 17, 17f, 76 in 30 nm fi ber, 998, 1000f oxidation of succinate to fumarate in, 646–647 chiral molecules, 17, 17f, 76–77 transcription-associated changes in, products of, 649f optical activity of, 18b, 77 1175–1176, 1176t pyruvate carboxylase reaction in, biotin and, chitin, 257, 258f, 262t transcriptionally active vs. inactive, 1175 651–653, 652f, 653f chloramphenicol, 1138, 1138s chromatography, 178 reactions of, 638–653, 654f chloride-bicarbonate exchanger, 398f, adsorption, 377f, 378 regulation of, 653–656 407–409, 407f affi nity, 91f, 92, 93t, 325–327, 325t allosteric and covalent mechanisms in, chloride ion channels column, 86–92, 90f 654–655, 654f in cystic fi brosis, 415b, 424 gas-liquid, 378 exergonic steps in, 655 in signaling, 468 high-performance liquid, 92 glyoxylate cycle in, 658–659, 658f, 659f chloride ion concentration, in cytosol vs. ion-exchange, 90, 91f, 93t multienzyme complexes in, 655–656, 655f extracellular fl uid, 465t in lipid analysis, 378 role of, in anabolism, 650, 651f chloroform, in lipid extraction, 377–378, 377f size-exclusion, 91f, 92 steps in, 640–653 chlorophyll(s), 771 thin-layer, 377f, 378 chemical logic of, 638–640 antenna, in light-driven electron fl ow, 778, chromatophore, 786 urea cycle links to, 706–708, 707f 781–782, 781f chromosomal scaffold, 999, 1000f citrulline, 81, 82s in light absorption, exciton transfer and, chromosome(s), 979–985 ClϪ. See chloride entries 774–775, 775f aneuploid, 1045b Claisen ester condensation, 376, 376f, 513, in photosynthesis, 771–773, 772f, 773f artifi cial, 985 513s, 674 chlorophyll a, 772s bacterial artifi cial, 319, 320f clathrates, 52 chloroplast(s), 6, 7f, 800, 801f cell-cycle changes in, 994, 994f clathrin, 1146, 1146f ATP synthase in, 787–788, 788f condensation of, 994, 995f, 1000–1002, Clausius, Rudolf, 22b ATP synthesis in, 732. See also ATP synthesis 1002f clavulanic acid, 224 evolution of, 788–789 daughter, 484 climate change, 816b–817b fatty acid synthesis in, 839, 840f defi nition of, 994 clonal selection, 175 integration of photosystems I and II in, 779–781 elements of, 979–985 clone(s), 178 lipid metabolism in, 839, 840f eukaryotic, 981–983, 983f defi nition of, 314 membrane lipids of, 365, 365f genes in, 979, 980. See also gene(s) in DNA libraries, 332f NADPH synthesis in, 839 partitioning of, in bacteria, 1025 cloned genes, expression/alteration of, photosynthesis in, 769–770, 770f replication of, 994, 994f 321–325, 322f electron fl ow in, 770 segregation of, errors in, 1045b cloning, 314–325 protein targeting to, 1142–1143 structure of, 994–1003 in bacteria, 314–325 starch synthesis in, 819 yeast artifi cial, 320, 321f, 985 blunt ends in, 316 chloroplast DNA (cpDNA), 983 chylomicrons, 669, 865–866, 865f, 865t, 867f cDNA in, 300f, 1087, 1096b–1097b

cholecalciferol (vitamin D3), 373, 373f, 373s molecular structure of, 669f DNA cleavage in, 314–317, 315f, 315t, 317f cholecystokinin, 698 chymotrypsin, 698 DNA fragment size in, 316 cholera toxin, 442b–443b catalytic activity of, 200, 210f, 214–218, DNA ligases in, 314, 315f, 316–317, 317f cholesterol, 368–370, 368f. See also sterol(s) 215f–217f electroporation in, 318 esterifi cation of, 864, 864f reaction mechanism of, 216f–217f, 515 enzymes in, 315t excess production of, 872b–873b structure of, 115f, 214, 214f fusion proteins in, 325 fates of, 864, 864f, 874–875 synthesis of, proteolytic cleavage in, gene expression and, 321–325, 322f in isoprenoid synthesis, 875f 231–232, 232f host organisms in, 322–323, 322f membrane, 386f, 386t chymotrypsinogen, 232f, 698 linkers/polylinkers in, 316–317, 317f distribution of, 389f cimetidine (Tagamet), 909 oligonucelotide-directed mutagenesis and, microdomains of, 398–399, 399f ciprofl oxacin, 992b, 992s 324, 325f BMInd.indd Page I-9 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-9

polymerase chain reaction in, 327–331, 328f Collins, Francis, 339, 339f coumarins, 992b procedures used in, 314, 315f Collip, J. B., 931b coumermycin A1, 992b restriction endonucleases in, 314–317, 315f, colon cancer, 1038b coupling, operational defi nition of, 748 315t, 317f mutations in, 493f covalent bonds, 9 site-directed mutagenesis and, 323–324 color vision, 480, 481b in enzymatic reactions, 195 steps in, 314, 315f column chromatography, 86–92. See also heterolytic cleavage of, 512, 512f sticky ends in, 316–317, 317f chromatography homolytic cleavage of, 512, 512f transformation in, 318 combinatorial control, 1158–1159, of phosphorus, 515–516, 515f cloning vectors, 314, 315t, 317–321, 318f–322f 1177, 1177f covalent catalysis, 200 bacterial artifi cial chromosome, 319, 320f comparative genomics, 39, 333, 345–347 covalent modifi cation, of regulatory enzymes, 226, in DNA library creation, 332 competitive inhibitor, 207–208, 208f, 228–235, 229f, 231t, 232f expression, 321–325 209f, 209t COX (cyclooxygenase), 845 lambda phage, 315t, 317 complementary DNA. See cDNA (complementary COX inhibitors, 845–847, 846f plasmid, 317–319, 319f, 320f DNA) COX4, 761, 761f shuttle, 320 Complex I (NADH: ubiquinone oxidoreductase) cpDNA (chloroplast DNA), 983 yeast artifi cial chromosome, 319–320, 320 fl ow of electrons and protons through, 744f Crassulaceae, photosynthesis in, 818 closed-circular DNA, 986–987, 987f in oxidative phosphorylation, 738, 739f creatine, 521s, 906, 946b–947b, 947s linking number for, 988–989, 988f, 996 Complex II (succinate dehydrogenase) amino acids as precursors of, 906–907 closed system, 21 fl ow of electrons and protons through, 744f biosynthesis of, 908f Clostridium acetobutyricum, in oxidative phosphorylation, 740, 740f in muscle, 945f, 946b–947b, 947 in fermentation, 551 Complex III (ubiquinone: cytochrome c creatine kinase, 526, 708b Clostridium botulinum, 401–402 oxidoreductase), 741f creatinine, 946b–947b CMP (cytidine 5Ј-monophosphate), 283s, 853 fl ow of electrons and protons through, 774f CREB (cyclic AMP response element binding

CO2. See carbon dioxide in oxidative phosphorylation, 740–742, 741f protein), 610 CoA (coenzyme A), 307, 307f. See also specifi c Complex IV (cytochrome oxidase), 742–743, 742f Creutzfeldt-Jakob disease, 150b–151b type, e.g., succinyl-CoA fl ow of electrons and protons through, 744f Crick, Francis, 97, 126, 287, 287f, 288–289, 977, coactivators, 1178–1179 path of electrons through, 742f 1011, 1092, 1092f, 1104 coagulation complex transposons, 1049 crocodile, movement of, 564b regulatory cascade in, 232 concentration gradient, 402, 403f crossing over, 1043, 1043f selectins in, 402 in membrane polarization, 464–465, 464f errors in, aneuploidy and, 1045b zymogens in, 232–235, 232f, 233f concerted inhibition, 900 CRP. See cAMP receptor protein (CRP) coagulation factors, 233, 234 concerted model, of protein-ligand binding, cruciform DNA, 292, 292f, 989, 990f defi ciency of, 234 167–168, 170f crude extract, 89 coated pits, 1146, 1146f condensation, 69, 69f cryptochromes, 536

cobalamin. See vitamin B12 (cobalamin) chromosomal, 994, 995f crystal structures, bound water molecules in, cobrotoxin, 426 in peptide bond formation, 86, 86f 54–55, 55f coding strand, in transcription, 1059, 1059f condensation reaction, 65 CTP, in ATCase synthesis, 227, 227f CODIS database, 330b, 330t condensins, 1002 CTR1, 475, 475f codon(s), 1104f, 1105 cone cells, 477–480, 477f, 480f culture, mammalian cell, 323 assignment of, 1106, 1107f in color vision, 480, 480f cyan fl uorescent protein (CFP), 448b–449b variations in, 1108b–1109b confi guration, 16 cyanobacteria, 5 base composition of, discovery of, 1105 isomeric, 16–18, 16f, 17f evolution of, 36, 37f base sequences in, discovery of, 1105–1106 vs. conformation, 248 nitrogen fi xation by, 882 dictionary of, 1107, 1107f conformation phosphorylation/photophosphorylation in, 789, initiation, 1107, 1107f boat, 249f 789f, 790f in protein synthesis, 1127–1129, 1129f chair, 249f cyanocobalamin, 680b reading frame for, 1105, 1105f, 1111 molecular, 19, 19f cyclic AMP. See cAMP (adenosine 3Ј,5Ј-cyclic termination, 1107, 1107f, 1108b–1109b native, 31, 116 monophosphate) codon bias, 1109b protein, 115–116 cyclic GMP. See cGMP (guanosine 3Ј,5Ј-cyclic coelacanth, anaerobic metabolism of, 564b vs. confi guration, 248 monophosphate) coenzyme(s), 3, 190, 191t. See also enzyme(s) conjugate acid-base pairs, 61, 61f cyclic nucleotide phosphodiesterase, 439f, 445 examples of, 190t as buffer systems, 64, 64f, 65–66 cyclin, 484f, 485 fl avin nucleotide, 536t conjugate redox pair, 528 degradation of, 486–487, 486f, 1148 NADϩ or NADPϩ as, stereospecifi city of dehydro- electron transfer of, 530–531, 530f synthesis of, 487 genase employing, 534t conjugated proteins, 89, 89t cyclin-dependent kinase complex, 484–488, prosthetic group, 190 consensus sequences, 104, 105b 485f, 486f in pyruvate dehydrogenase complex, 634–635, oriC, 1020–1021, 1020f cyclin-dependent protein kinase(s), 636f of promoters, 1060, 1061f, 1157, 1157f 485–488, 485f as universal electron carrier, 532 of protein kinases, 230–231, 231t in cell cycle regulation, 485–488, 485f coenzyme A (CoA), 307, 307f. See also specifi c consensus tree of life, 108f inhibition of, 487 type, e.g., succinyl-CoA conservation of energy, 21, 21f oscillating levels of, 451–452, 452f

coenzyme B12, 678, 680f–681f constitutive gene expression, 1156 phosphorylation of, 485–486, 485f, 486f, 488f coenzyme Q, 375, 375s, 735, 735f, 735s contig, 342 regulation of, 485–486, 485f–487f coenzyme reduction, stoichiometry of, 649t contractile proteins, 179–184, 180f–183f synthesis of, 487 cofactors, enzyme, 190, 190t cooperativity, binding, 163–169, 165f, 166f cyclin-dependent protein kinase 9, 1068 Cohen, Stanley, 313, 313f copper ions, in Complex IV, 742, 742f cycloheximide, 1138, 1139s cohesins, 1000 Corey, Robert, 117f, 120, 126, 133 cyclooxygenase (COX), 845 coiled coils Cori, Carl F., 564b, 616b, 616f, 621 cyclooxygenase (COX) inhibitors, collagen as, 126f, 127 Cori, Gerty T., 564b, 616b, 616f, 621 845–846, 846f -keratin as, 126, 126f Cori cycle, 564b, 568–569, 948, 948f cycloserine, 907 cointegrate, 1049 Cori disease, 617t cystathionine -synthase, 894 collagen Cornforth, John, 862, 863f cystathionine -lyase, 894 amino acids in, 127–130, 127f, 128b–129b coronary artery disease cysteine, 10s, 79s, 81, 81s, 715, 894 ascorbic acid and, 128b–129b hyperlipidemia and, 871–874, 872b–873b biosynthesis of, 892–894, 895f disorders of, 128b–129b trans fatty acids and, 361 degradation of, to pyruvate, 715, 715f proteoglycans and, 266 corrin ring system, 680b properties of, 77t, 81 structure of, 124f, 126t, 127–130, 127f corticosteroids, 372, 372f, 372s, 933t, 935. See also cystic fi brosis triple helix of, 124f, 126t, 127–130, 127f, under steroid hormone(s) defective ion channels in, 415b, 424 128b–129b synthesis of, 874, 874f, 875f protein misfolding in, 149, 151 types of, 127 cortisol, 372, 372s, 851s, 937, 958–959 cystine, 81, 81s colligative properties, solute concentration in glucose metabolism, 851 cytidine, 283s and, 55, 56f cotransport systems, 409, 409f cytidine diphosphate (CDP), 853, 853f BMInd.indd Page I-10 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-10 Index

cytidine 5Ј-monophosphate (CMP), 283s, 853 dehydrohydroxylsinonorleucine, 130s dideoxy method, for DNA sequencing, 302–304, cytidylate, 282t, 283s deletion mutations, 1027 303f, 304f cytidylate synthetase, 916 DG (free-energy change). See free-energy dideoxyinosine (DDI), 1089b cytochrome(s), 735 change (DG) dideoxynucleotides, in DNA sequencing, 302–304, prosthetic groups of, 735, 736f DS (entropy change), 23 303f, 304f

cytochrome b5, 843 denaturation dielectric constant, 50 cytochrome b5 reductase, 843 of DNA, 297–298, 297f, 298f 2,4-dienoyl-CoA reductase, 677 cytochrome bc1 complex, 738t, 740–742, of proteins, 143–146, 144f differential centrifugation, 8, 8f 741f. See also Complex III of RNA-DNA hybrids, 298 diffusion

cytochrome b6 f complex, 781–783, 782f denaturation mapping, 1012 facilitated, 403–404, 404f. See also cytochrome b6 f, dual roles of, 790f dendrotoxin, 426 transporter(s) cytochrome c denitrifi cation, 882 hop, 398 absorption spectra of, 735, 736f 2-deoxy--D-ribose, 10s of membrane lipids, 396–398, 396f–398f in apoptosis, 764–765, 764f -2Ј-deoxy-D-ribofuranose, 284f simple, 403, 403f, 404f structure of, 133t 2-deoxy-D-ribose, 244s, 282 of solutes, 402–404, 403f, 404f. See also cytochrome f, water chain in, 54–55, 55f deoxyadenosine, 283s membrane transport cytochrome oxidase, 742. See also deoxyadenosine 5Ј-monophosphate (dAMP), 283s difl uoromethylornithine (DFMO), for African Complex IV 5Ј-deoxyadenosyl group, 680 sleeping sickness, 211b–212b subunits of, 742f 5Ј-deoxyadenosylcobalamin, 678, 680b digestive enzymes, 697–699, 698f cytochrome P-450, 763–764, 844b, 935, 943 deoxyadenylate, 283s dihedral angles in secondary structures, mitochondria and, 763 deoxycytidine, 283s 123–124, 124f in xenobiotics, 763–764 deoxycytidine 5Ј-monophosphate (dCMP), 283s dihydrobiopterin reductase, 720 cytoglobin, 163 deoxycytidylate, 283s dihydrofolate reductase, 920 cytokines, 457 deoxyguanosine, 283s substrate binding to, 195f in cell cycle regulation, 486f, 487 deoxyguanosine 5Ј-monophosphate (dGMP), 283s dihydrogen phosphate, as buffer, 62–63, 63f cytoplasm, 3, 3f deoxyguanylate, 283s dihydrolipoyl dehydrogenase, 635 fi laments in, 8–9, 8f deoxynucleoside triphosphates, regulation of dihydrolipoyl transacetylase, 635 cytosine, 10s, 282, 282t, 283f. See also ribonucleotide reductase by, 918–919, 936f dihydroxyacetone, 244, 244s, 246s pyrimidine bases deoxyribonucleotides, 30, 282t, 283, 283f. dihydroxyacetone phosphate, 198, 550, deamination of, 299, 300f See also nucleotides 550s, 562s methylation of, 302 ribonucleotides as precursors of, 917–920, in Calvin cycle, 805, 806f, 808f, 809 cytoskeleton, 8–9, 8f 917f, 936f in glyceroneogenesis, 850 cytosol, 3, 3f deoxythymidine, 283s in glycolysis, 544–546

cellulose synthesis in, 822–823 deoxythymidine 5Ј-monophosphate (dTMP), 283s Pi exchange for, 809–810, 809f, 810f contents of, 10, 11f deoxythymidylate, 283s transport of, 809–810, 810f lipid synthesis in, 839, 840f depurination, 300, 300f 1,25-dihydroxycholecalciferol, 373, sucrose synthesis in, 819–820 dermatan sulfate, 261 373s, 933t

cytotoxic T cells (TC cells), 175, 175t desaturases, 842–845, 843f 1,25-dihydroxycholecalcitriol, 935 desensitization, receptor, 434, 434f, 443–446, 445f dimethylallyl pyrophosphate, in cholesterol desmin, 181 synthesis, 861, 861f, 862f D desmosine, 81, 82s dimethylnitrosamine, as mutagen, 301f, 302 D arm, of tRNA, 1118, 1119f desolvation, in enzymatic reactions, 198, 198f dimethylsulfate, as mutagen, 301f, 302 D isomers, 245 development dinitrogenase, 883 D, L system of stereochemical nomenclature, 18, gene regulation in, gene silencing in, dinitrogenase reductase, 883 76f, 78, 245 1185–1186, 1185f Dintzis experiment, 1127 dabsyl chloride, 98–100, 98s pattern-regulating genes and, 1188–1191 dioxygenases, 844b Dalgarno, Lynn, 1127 dexamethasone, 851s diphtheria toxin, 1139 daltons, 14b in glucose metabolism, 851 dipole-dipole interactions, 117 Dam, Henrik, 374, 375f dextran, 256, 258f, 262t. See also polysaccharide(s) direct transposition, 1049, 1050f Dam methylase, 1019t, 1020 synthetic, 256 disaccharides, 243, 252–253. See also in mismatch repair, 1029 dextrose, 243, 244s. See also glucose carbohydrate(s); oligosaccharide(s) dAMP (deoxyadenosine 5Ј-monophosphate), 283s DGDG (digalactosyldiacylglycerol), 365, 365f conformations of, 257–259, 258f, 259f dansyl chloride, 98–100, 98s dGMP (deoxyguanosine 5Ј-monophosphate), 283s formation of, 252, 252f databases diabetes insipidus, 408b hydrolysis of, 252–253 for DNA fi ngerprinting, 330b, 330t diabetes mellitus, 959–960 to monosaccharides, 558–560, 560f genomic, 342, 348–349 acidosis in, 67 nomenclature of, 252–253 for protein structure, 115f, 138–140, 139f–140f defective glucose and water transport in, 408b oxidation of, 252–253 daughter chromosomes, 484 diagnosis of, 250b–251b, 960 reducing, 252–253 Dayhoff, Margaret Oakley, 76, 76f early studies of, 931b structure of, 252–253, 252f, 253f

dCMP (deoxycytidine 5Ј-monophosphate), 283s fat metabolism in, 559f dissociation constant (acid) (Ka), 61f–63f, 62–63 DDI, 1089b fatty acid synthesis in, 849–850 dissociation constant (Kd), 160–162, 161t De Duve, Christian, 617b glucose metabolism in, 558, 559f, 957f, 959–960 for enzyme-substrate complex, 204 de novo pathways, 910–922 glucose testing in, 250b–251b in Scatchard analysis, 435b deamination ketosis/ketoacidosis in, 688, 711, 959–960 dissociation energy, 48 of nucleotide bases, 299–300, 300f mature onset of the young, 611b–612b distal His, 163 oxidative, 700 mitochondrial mutations and, 768 disulfi de bonds, in amino acid sequencing, debranching enzyme, 560, 614 pathophysiology of, 959–960 99–100, 99f decarboxylation sulfonylurea drugs for, 954 divergent evolution, 644 of amino acids, 908–909, 910f treatment of, 852, 954, 964–965 of -oxidation enzymes, 683–684 free radical-initiated, 514–515, 515f type 1, 611b, 959 DNA, 15, 29, 31f. See also nucleic acids of -keto acid, 513s type 2, 611b, 959, 968–970 A-form, 291, 291f oxidative, 634 drug therapy for, 852, 970, 970t annealing of, 297–298, 297f degeneracy, of genetic code, 1107 insulin insensitivity in, 959, 964–965, 968–970 B-form, 291, 291f, 987 dehydration, of 2-phosphoglycerate to lipid toxicity hypothesis for, 969–970 bacterial, 981, 982f, 982t phosphoenolpyruvate, 554 diabetic ketoacidosis, 67, 688, 711, 960 packaging of, 1002–1003 dehydroascorbate, 129s diacylglycerol, 370, 447, 450f topoisomerases and, 990 7-dehydrocholesterol, 373, 373s in triacylglycerol synthesis, 849f base pairs in, 287, 287f, 288–290, 289f, 290f. See dehydrogenase, 529 diacylglycerol 3-phosphate, in triacylglycerol also base(s), nucleotide/nucleic acid; base stereospecifi city of, employing NADϩ or NADPϩ synthesis, 849, 849f pairs/pairing as coenzymes, 532–535, 534t dialysis, protein, 90 Chargaff’s rules for, 288 dehydrogenation, 529 diastereomers, 17, 17f chemical synthesis of, 304, 305f oxidations involving, 529–530, 529f dichromats, 480 chloroplast, 983 BMInd.indd Page I-11 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-11

cleavage of, 314–317, 315f specifi c linking difference for, 988 DNA polymerase I, 1016, 1016f, 1017 blunt ends in, 316, 317f stability of, 35 discovery of, 1013 restriction endonucleases in, 314–317, 315f, strand length in, 981–983, 982f–983f functions of, 1016, 1023t 315t, 317f supercoiling of, 985–994, 987f, 996, 996f large (Klenow) fragment of, 1017 sticky ends in, 316–317, 317f chromatin assembly and, 997f in nick translation, 1017, 1017f closed-circular, 986–987, 987f condensins and, 1002, 1002f structure of, 1016f, 1017 coding, 984 degree of, 987f DNA polymerase II, 1016, 1016t compaction of, 994–1000, 1002f negative, 989, 989f DNA polymerase III, 1016, 1016t, 1017, 1018t, complementary. See cDNA (complementary plectonemic, 992–993, 994f 1021–1022, 1023f DNA) positive, 989, 989f functions of, 1023t damaged, 1027–1038, 1036f. See also DNA solenoidal, 993, 994f, 996 in mismatch repair, 1030, 1031f repair; mutation(s) topoisomerases and, 989–990, subunits of, 1016t, 1017t, 1018f error-prone translesion DNA synthesis and, 990f, 991f DNA polymerase IV, 1016, 1037 1034–1037 in transcription, 1058f DNA polymerase V, 1016, 1036–1037 repair of. See DNA repair superhelical density of, 988 DNA polymerase , 1026 SOS response and, 1035, 1036t, superhelix of, 987f DNA polymerase , 1026 1169–1170, 1169f synthesis of. See DNA replication DNA polymerase , 1037, 1037b–1038b degradation of, 1013 template strand of, in transcription, DNA polymerase , 1037 denaturation of, 297–298, 298f, 300f 1058f, 1059, 1059f DNA polymerase , 1037 denaturation mapping of, 1012 topoisomers of, 989, 990, 990f DNA primases, 1018, 1019t, 1021, 1022f double helix of, 288–290, 289f, 290f. See also topology of, 986 DNA profi ling, 329–330 DNA structure in transcription, 31f DNA recombination, 1038–1052 supercoiling and, 985–994, 987f. See also as transcriptional template, 1058f, 1059 in bacteria, 1039–1041 DNA, supercoiling of viral, 980–981, 982t, 1026–1027 branch migration in, 1040–1041, 1042f in transcription, 1058f weak interactions in, 286–287, 287f, 289, crossing over in, 1043, 1043f–1044f underwinding of, 987, 987f 289f, 290f in DNA repair, 1039–1041, 1044f unwinding of/rewinding of, 297–298, 297f, yeast, 981, 982t double-strand break repair model for, 298f, 1012–1013, 1013f. See also DNA Z-form, 291, 291f 1043–1046, 1044f replication DNA amplifi cation, by polymerase chain reaction, in eukaryotes, 1041–1043 variations of, 290–291, 291f 327–331, 328f functions of, 1039 double-strand breaks in DNA-binding domains/motifs homologous genetic, 1038–1046 in recombination, 1043–1046, 1052f in gene regulation, 1160–1163, 1162f functions of, 1039, 1043 repair of, 1038–1046, 1044f, 1052f helix-turn-helix, 1162 site-specifi c, 1038, 1046–1049, 1047f, 1048f early studies of, 288–290, 288f–290f homeodomain, 1163, 1163f in immunoglobulin genes, 1049–1051, 1051f, 1052f enzymatic degradation of, 1013 zinc fi nger, 1162–1163, 1163f meiosis events and, 1039–1041, 1043f eukaryotic, 981–983, 982t DNA-binding proteins, 1017, 1019f site-specifi c, 1038, 1046–1049, 1047f, 1048f evolutionary stability of, 29 DNA cloning. See cloning transposition in, 1049, 1050f folding of, 998–999 DNA-dependent RNA polymerase, 1058–1060, DNA repair, 1027–1038 highly repetitive, 984 1058f, 1157 in bacteria, 1028t histones and, 994–1000, 996f DNA-dependent transcription, 1058–1069. base-excision, 1028t, 1030–1031, 1032f human, 981–983, 982t See also transcription cancer and, 1037b–1038b hybridization of, 298–299, 300f DNA fi ngerprinting, 329–330 cyclin-dependent protein kinases in, 486, 488, 488f hydrophilic backbone of, 285, 285f, 288 DNA genotyping, 329b–330b direct, 1032–1033, 1034f junk, 1096b DNA glycolases, in base-excision repair, DNA photolyases in, 1028t, 1032–1033, 1034f light absorption by, 297–298 1030–1031, 1032f error-prone translesion DNA synthesis in, linker, in nucleosome, 995f DNA gyrase, 1019t, 1023t 1034–1037, 1036t linking number of, 988–989, 988f, 996 DNA helicase II, in mismatch repair, 1030 mismatch, 302, 1015, 1028–1030, 1028t, topoisomerases and, 989–990, 991f DNA helix. See DNA, double helix of 1029f–1031f melting point for, 298, 298f DNA hybridization, cDNA in, 299, 300f, 1087 nick translation in, 1017, 1017f, 1018, 1023, methylation of, 302 DNA library, 332, 332f, 1096b–1097b 1024f, 1028t, 1031–1032, 1033f mitochondrial, 765–768, 765f, 983, 1108b–1109b. specialized, 334, 335f nucleotide-excision, 1028t, 1031–1032, 1033f, See also mitochondria; mtDNA DNA ligases, 314, 315f, 315t, 317f, 1018, 1023t 1037b–1038b aging and, 766 in mismatch repair, 1030, 1031f O6-methylguanine-DNA methyltransferase in, mutagenic changes in in nick translation, 1017f, 1018, 1023, 1023f, 1033, 1035f from alkylating agents, 301f, 302 1028t, 1031–1032, 1033f phosphorylation in, 486, 488, 488f from nitrous acid, 301, 301f DNA metabolism, 1009–1052. See also DNA proofreading in, 1015, 1016f from radiation, 300, 301f recombination; DNA repair; DNA replication recombinational, 1039–1041, 1044f noncoding regions of, 342–344, 984. See also nomenclature of, 1010 SOS response in, 1035, 1036t, 1169–1170 introns overview of, 1009–1010 TLS polymerases in, 1034–1037, 1037b–1038b nontemplate (coding) strand of, in transcription, DNA microarrays, 337–338, 337f, 338f DNA replicase system, 1017 1058f, 1059 DNA mismatch repair, 302, 1028–1030, DNA replication, 30, 31f, 1011–1027 nucleosomes and, 994, 995–1000, 996f, 997f, 1029f–1031f accuracy of, 1015, 1016f 1000f, 1175–1176. See also nucleosomes DNA photolyases, 1028t, 1032–1033, 1034f automated, 304, 304f, 305f nucleotides of, 282t, 283–284, 283f. See also reaction mechanism of, 1034f in bacteria, 1011–1025, 1013–1026, 1015–1025, nucleotide(s) DNA polymerase(s), 303f, 315t, 327 1015f–1025f packaging of, 979, 979f, 985–994, 994–995. See in base-excision repair, 1037 base pairing in, 1013, 1014f, 1015, 1015f also DNA, supercoiling of dissociation/reassociation of, 1014 base stacking in, 1013, 1014f in bacteria, 1002–1003, 1003f 5Јn3Ј exonuclease activity of, 1017 chain elongation in, 1013–1014, 1014f, 1019t, in eukaryotes, 994–1000, 1001f functions of, 1016–1017, 1023t 1021–1022, 1021f–1024f, 1022f phosphodiester linkages in, 284–285, 285f in nick translation, 1017 directionality of recognition sequences in, 315, 315t processivity of, 1014 in bacteria, 1012–1013, 1013f recombinant, 314. See also cloning proofreading by, 1015, 1016f in eukaryotes, 1026 regulatory sequences in, 980 properties of, 1016t, 1018t DNA-binding proteins in, 1017, 1019f relaxed, 985, 987f, 989f, 1019 reaction mechanism of, 1014f enzymology of, 1013–1017, 1014f, 1023t. See repetitive, 984–985 in replication, 1013–1017. See also replication also DNA polymerase(s) and specifi c centromeric, 984, 984f in bacteria, 1011–1025 enzymes telomeric, 984–985, 984f in eukaryotes, 1026 error-prone translesion, 1034–1037, 1036t replication of, 30, 31f RNA-dependent, 1085–1094, 1086f in eukaryotes, 1025–1026 satellite, 984 template for, 1014f helicases in, 1017, 1020f simple-sequence, 344, 984 3Јn5Ј exonuclease activity of, 1015f, 1017 initiation of, 1019–1021, 1019t, 1020f as single molecule, 30 types of, 1016–1017, 1016t, 1018t lagging strand in, 1013, 1013f size of, 981–983, 982f–983f viral, 1026–1027 synthesis of, 1021–1022, 1022f BMInd.indd Page I-12 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-12 Index

DNA replication (Continued) DNA synthesis. See DNA replication eicosanoids, 371–372, 371f, 845, 933t, 935. leading strand in, 1012, 1013f DNA transposition. See transposition See also leukotriene(s); prostaglandin(s); synthesis of, 1021–1022, 1022f DNA unwinding element (DUE), 1019 thromboxane(s) mistakes in, 1015, 1016f DNA viruses, 980–981, 1026–1027 in signaling, 847 nick translation in, 1017, 1017f, 1018, 1023, DnaA protein, in replication initiation, 1019t, synthesis of, 845–847, 846f 1023f, 1024f 1020, 1020f eicosatrienoate, synthesis of, 842f nucleophilic attack in, 1013, 1014f DnaB helicase eIF4E binding proteins, 1184 Okazaki fragments in, 1012–1013, 1013f, in chain elongation, 1022f Einstein, Albert, 222 1021–1022, 1021f, 1022f in mismatch repair, 1031f elasticity, of enzyme, 597b phosphorylation in, 1013, 1014f in replication initiation, 1019t, 1020, 1020f, elasticity coeffi cient (), 597, 597b primer in, 1014, 1014f, 1017–1018 1021–1022, 1023t enzyme response and, 597, 597f proofreading in, 1015, 1016f DnaC protein, in replication initiation, 1019t, elastin, proteoglycans and, 266 rate of, in eukaryotes, 1025–1026 1020, 1020f electrical charge replication fork in, 1012, 1013f, 1021–1023 DnaG protein, 1019t, 1021, 1023t of amino acids, 84 in bacteria, 1012, 1013f, 1021–1023, 1021f DnaK/DnaJ, in protein folding, 147 pH and, 84 in eukaryotes, 1025–1026, 1030f DNases, 1013 electrical potential energy, of proton-motive repair of, 1039–1041, 1044f. See also DNA Dobzhansky, Theodosius, 32 force, 744f repair dodecanoic acid, 358t electrochemical gradient (electrochemical stalled, 1024–1025, 1036f Doisy, Edward A., 374, 375f potential), 403, 403f replisomes in, 1017, 1022, 1023 dolichols, 375, 375s free-energy change for, equation in, 744 reverse transcriptase in, 1086–1087 domains, 137 in membrane polarization, 464–465, 464f RNA-dependent, 1085–1094. See also RNA microdomains, 398–399 electrogenic transport, 410 replication dopamine, 909 electrolytes, plasma levels of, 950 rules of, 1011–1013 double-displacement mechanism, 207, 207f electromagnetic radiation, 771, 771f semiconservative, 1011 double helix, 30, 31f electromotive force (emf), 528 site-specifi c, 1046–1049 DNA, 288–290, 289f, 290f. See also DNA electron(s) strand synthesis in, 1013, 1013f structure reduction potential affi nity for, 530–531, structural aspects of, 289–290, 290f supercoiling and, 985–994, 987f. See also 530f, 531t template for, 1011, 1014f DNA, supercoiling of transfer of, 528–529 Ter sequences in, 1023–1025, 1024f in transcription, 1058f electron acceptors termination of, in bacteria, 1023–1025 underwinding of, 987, 987f pyruvate as, in lactic acid fermentation, topoisomerases in, 989–990, 990, 990f, 991f, unwinding of/rewinding of, 297–298, 297f, 563–565 999, 1017 298f, 1012–1013, 1013f. See also DNA universal, 734–735, 734t Tus-Ter complex in, 1023–1025, 1024f replication electron carriers. See also electron-transfer vs. transcription, 1058 variations of, 290–291, 291f reactions, mitochondrial DNA replication origin (oriC), 1020–1021, 1020f RNA, 294–295, 294f, 295f soluble, NADH and NADPH as, 532–535, in bacteria, 1012 double-reciprocal plot, 203, 204b 533f, 534t DNA sequences, in genome, 342–345, 343f, 344f for enzyme inhibitors, 209b specialized, 532 DNA sequencing, 302–304, 303f, 304f double-strand break universal, coenzymes and proteins as, 532 automated, 304, 304f error-prone translesion DNA synthesis repair electron fl ow next-generation, 304, 339–342, 341f, 342f for, 1046 light-driven, 776–786 pyrosequencing, 339–341, 341f in recombination, 1043–1046, 1044f, acting in tandem, 779–781 reversible terminator, 341–342, 342f 1051, 1052f antenna chlorophylls in, 778, 781–782, 781f shotgun, 341–342 recombinational DNA repair for, 1039–1041, in chloroplasts, 770

DNA structure, 30–31, 287–293 1044f cytochrome b6 f complex and, 781–783, 782f antiparallel orientation in, 289 double-strand break repair model, 1051 kinetic and thermodynamic factors in, 778–779 in bacteria, 1003f, 1037b–1038b Down syndrome, 1045b reaction centers in, 776–778, 778f base stacking in, 286–287, 288–289, doxorubicin (Adriamycin), 993b, 993s water split in, 784–785 289f, 290f Drosophila melanogaster proton gradient in, 786–787, 788f

chromosomal scaffolds and, 999, 1000f development in through cytochrome b6 f complex, 782f compacted, 994–1000, 1002f gene regulation in, 1186–1191 electron pushing, 216, 216f cruciforms in, 292, 292f, 989, 990f pattern-regulating genes in, 1188–1191 electron-transfer reactions early studies of, 288–290, 288f–290f genome of, 981, 982t ATP synthesis in, 747–750, 748f folding in, 998–999, 1000f life cycle of, 1186–1187, 1189f mitochondrial, 732–747 functional correlates of, 288, 289–290, 290f drug metabolism, cytochrome P-450 in, alternative mechanism of NADH oxidation in, hairpins (loops) in, 292, 292f, 999, 1000f 844b, 943 746, 746b–747b in replication fork, 1012, 1012f drug resistance Complex I, 738, 738t, 739f helical. See DNA, double helix of ABC transporters and, 413–414 Complex II, 740, 740f Hoogsteen positions/pairings in, 292, 293f plasmids in, 981 Complex III, 740–742, 741f inverted repeats in, 291–292, 292f drug therapy. See specifi c drugs Complex IV, 742–743, 742f linking number and, 988–989, 988f, 996 dTMP (deoxythymidine 5Ј-monophosphate), 283s in multienzyme complexes, 737–743 major/minor groove and, 289, 289f dynamic steady state, 21 in plants, 746 mirror repeats in, 292, 292f dyneins, 179 through membrane-bound carriers, 735–737, palindromes in, 291–292, 292f 736f, 737f, 737t primary, 287–288 protein components of, 737–738, 738t ribbon model of, 989f E proton gradient conservation of energy in, secondary, 287 EЊ (standard reduction potential), 530 743–745, 744f strand complementarity in, 289–290 of biologically important half-reactions, 531t universal electron acceptors in, 734–735, 734t strand separation in, 987–989, 987f in calculating free-energy change, 531–532 electron-transferring fl avoprotein (ETF), 674 supercoiling and, 985–994. See also DNA, measurement of, 530 electronegativity, atomic, 216 supercoiling of E (exit) binding site, ribosomal, 1128 electroneutral transport, 409 tertiary, 288, 979 E. coli. See Escherichia coli electrophiles, in enzymatic reactions, 216f, tetraplex, 292 E1/2/3 enzymes, in protein degradation, 1147, 512, 512f three-dimensional, 290–291 1147f, 1148 electrophoresis, 92–95, 93f topoisomerases and, 989–990, 990f eating, hormonal control of, 960–968 in cloning, 320 triplex, 292, 293f Edelman, Gerald, 175 in DNA sequencing, 302–304, 303f, 304f, 305f twist in, 989 editing, mRNA, 1075–1076, 1111–1113 polyacrylamide gel, 93–94, 93f underwinding and, 987, 987f Edman, Pehr, 98 pulsed fi eld gel, 320 variations in, 290–293, 291f Edman degradation, 98–100, 98f two-dimensional, 94, 95f Watson-Crick model for, 288–290, 289f, 290f effectors, 1157 electroporation, 318 writhe in, 989 Ehlers-Danlos syndrome, 130 electrospray ionization mass spectrometry, x-ray diffraction studies of, 288, 289, 289f eicosanoic acid, 358t 101, 101f BMInd.indd Page I-13 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-13

electrostatic interactions, with water, 50, 51f enthalpy (H), 23, 506 adenylation of, 229f elements, essential, 12, 12f enthalpy change (⌬H), 506–507 ADP-ribosylation of, 229, 229f elimination reaction, 513–514, 514f units of, 507t allosteric, 226–228, 227f, 228f Elion, Gertrude, 923, 923f, 1026 entropy (S), 21f, 22b–23b, 23, 506 conformational changes in, 226–227, 227f ELISA, 178f, 179, 932 increase in, 23 kinetics of, 227–228, 228f ellipticine, 993b, 993s negative, 23 in carbohydrate metabolism, 592–593, 593t elongation, 1129 protein stability and, 116 classifi cation of, 190–191, 191t elongation factors, 1129 solubility and, 51, 53, 53f in coagulation, 232–235, 232f, 233f transcriptional, 1066t, 1068 entropy change (⌬S), 23 coenzymes and, 3, 190, 191t. See also Elvehjem, Conrad, 535 entropy reduction, in enzymatic reactions, coenzyme(s) Embden, Gustav, 544 198, 198f cofactors for. See enzyme cofactor(s) embryonic development, gene regulation in, env, 1086f, 1087, 1088 contributing to fl ux, 596–597, 596f 1186–1191 enzymatic pathways, 28 debranching, 560, 614 gene silencing in, 1185–1186, 1185f enzymatic reaction(s), 27–28, 27f, 28f, 192–200 defi nition of, 190 embryonic stem cells, 1192 acid-base catalysis in early studies of, 190 enantiomers, 17, 17f, 77, 244 general, 199, 199f elasticity of, 597b monosaccharide, 244, 244f specifi c, 199 in fatty acid oxidation, 668–672, 670f–672f, 684f encephalomyopathy, mitochondrial, 767–768 activation energy of, 193, 195 evolution of, 683–684 endergonic reactions, 23, 25 binding energy of, 195–197 functions of, 27–28, 28, 28f coupled with exergonic reactions, 24–25, 24f bisubstrate, 206–207, 207f glycine cleavage, 894 Endo, Akira, 872b chymotrypsin-catalyzed, 200, 210f, 214–218, hepatic, 939–943 endocrine glands, 933, 936–937, 936f 215f–217f in hydrolysis reactions, 65 hormone release from, 936–937, 938f. See also coordinate diagram for, 192–193, 193f methylation of, 229, 229f hormone(s) covalent interactions in, 195 in nitrogenase complex, 882–888, 886f, 887f endocytosis, 8 desolvation in, 198, 198f nomenclature of, 190–191, 191t, 844b receptor-mediated, 868–869, 868f, 1146–1147, double-displacement (Ping-Pong) mechanism in, in nucleotide biosynthesis, chemotherapeutic 1146f 207, 207f agents targeting, 923–925, 923f, 924f endogenous pathways, 867 electron pushing in, 216, 216f overview of, 189–191 endomembrane system, 8 enolase-catalyzed, 220, 221f pH of, 210f, 212–213 endonucleases, 1013 entropy reduction in, 198, 198f pH optimum of, 67 in mismatch repair, 1029–1030 equilibria of, 192–194, 194t phosphorylation of, 229–231, 229f, 231t, 232f restriction. See restriction endonucleases evolution of, 33f, 34–35 prosthetic groups and, 190 endoplasmic reticulum, 6, 7f fi rst-order, 194 in protein degradation to amino acids, 696–699, fatty acid synthesis in, 840f, 842, 843 free-energy change in, 25–26, 192, 193f, 194, 698f lipid metabolism in, 840f, 842, 843 194t, 197–198 in protein folding, 147 oxidation of fatty acids in, 684–685, 685f ground state in, 192 proteolytic, regulation of, 231–232, 232f protein targeting in, 1140, 1141f hexokinase-catalyzed, 219–220, 220f purifi cation of, 93t, 95–96 endosymbiosis, 36 inhibition of in pyruvate dehydrogenase complex, 635–636 in eukaryotic evolution, 36, 37f competitive, 207–208, 208f, 209f, 209t receptor, 453–460. See also receptor enzymes endosymbiotic bacteria, chloroplast evolution from, reversible, 207–210, 208f, 209f, 209t in recombinant DNA technology, 315t 788–789 intermediates in, 217 in redox reactions, 844b–845b energy, 20–29 lysozyme-catalyzed, 220–222, 222f, 223f regulatory, 226–235 activation, 27, 27f, 193, 193f mechanism-based inactivators in, 210 allosteric, 226–228, 227f, 228f in membrane transport, 403–404, 404f metal ion catalysis in, 200 complex, 235 rate constant and, 194 noncovalent interactions in, 195 covalent modifi cation of, 226, 228–235, 229f, ATP, 306, 306f, 522–523, 523f, 577f pre–steady state, 202 231t, 232f binding, 195 in protein purifi cation, 93t, 95–96, 95f functions of, 226–227 biological transformations of, in rate of, 192–194, 193f. See also kinetics of, 227–228, 228f thermodynamics, 506–507, 507t enzyme kinetics phosphorylation and, 229–232, 229f, 231t, 232f bond dissociation, 48 acceleration of, 192–194, 194t proteolytic cleavage and, 231–234, 232f cellular, in oxidative phosphorylation measurement of, 207 unique properties of, 226 regulation, 760 rate constants for, 194, 203–205, 205t response of conservation of, 21, 21f rate equation for, 194 elasticity coeffi cient and, 597f, 598b–599b for dissolution, 51–52 rate-limiting steps in, 194, 203–205 to metabolite concentration, 593, 593t entropy and, 23, 25 reaction intermediates in, 193 restriction. See restriction endonucleases free. See free energy (G) regulation of, 226–235, 589–592. See also RNA, 34–35, 34f, 1069, 1070–1075, 1082–1085, Gibbs free, 506 enzyme(s), regulatory 1082f–1084f, 1092–1094, 1117b informational macromolecules requirement for, metabolic, 592–593 selectivity of, 28 524–525 in RNA processing, 1082–1085, 1082f–1084f in signaling, 434, 434f interconversion of, 21f steady-state, 202, 203–205 specifi city of, 197 light, chlorophyll absorption of, 771–773, steps in, 216–217, 216f–217f, 217f structure of, 190 772f, 773f suicide inactivators in, 210 turnover number for, 205, 205t oxidative, in citric acid cycle, 647–649, transition-state, 27, 193, 195–197, 217 ubiquitination of, 229 649f, 649t weak interactions in, 53, 53f, 54, 195–197, 196f in urea synthesis, 704–706, 705f, 706f potential, of proton-motive force, 744 enzymatic reaction mechanisms, 216–217, genetic defects and, 709–710, 710f of protein conformation, 116 216f–217f uridylylation of, 229f for protein folding, 116, 146, 146f chymotrypsin, 200, 210f, 215f–217f enzyme activity proton gradient conservation of, in mitochondrial defi nition of, 216 change in, in metabolite fl ux, 596f, 597, 597f electron-transfer reactions, 743–745, 744f enolase, 220, 221f factors determining, 589–592, 590f solar, 769, 770f hexokinase, 219–220, 220f enzyme cascade, 434, 434f, 621 sources of, 21 lysozyme, 220–222, 222f, 223f MAPK, 455, 456f energy-coupled reactions, 24–25, 24f Phillips, 221–222 in plants, 475–476, 475f energy metabolism, 588f enzyme(s), 27, 189–237, 190. See also specifi c enzyme cofactors(s), 190, 190t enolase, 554, 593t enzyme, e.g., glucose 6-phosphate adenosine as, 306–308, 307f catalytic activity of, 220, 221f dehydrogenase in amino acid catabolism, 712–715, 712f, 713f reaction mechanism of, 221f acetylation of, 229 lipids as, 370, 374–375 enoyl-ACP reductase, 837f, 838 active site of, 192, 192f enzyme inhibitors, 207–212, 208f, 209f trans-⌬2-enoyl-CoA, 673 activity of, 93t, 95–96, 96f, 192–200 competitive, 207–208, 208f, 209f, 209t enoyl-CoA hydratase, 674 catalytic, 27–28, 28f, 192–200. See also irreversible, 210–212 ⌬3,⌬2-enoyl-CoA isomerase, 677 catalysis; enzymatic reaction(s) mixed, 208, 208f, 209f enterohepatic circulation, 869 evolution of, 33f, 34–35 reversible, 207–208, 208f, 209f, 209t enteropeptidase, 698 specifi c, 93t, 95–96, 96f uncompetitive, 208, 208f, 209f, 209t BMInd.indd Page I-14 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-14 Index

enzyme kinetics, 200–213 glycophorin in, 390, 390f genome sequencing and, 349–350, 349f, 350f comparative, 205 membrane proteins of, 390, 390f genomics and, 37–38, 38t, 345–347, 346f, initial velocity and, 200–201, 201f shape of, 173f 349–350 maximum velocity and, 201–205, 201f synthesis of, JAK-STAT pathway in, horizontal gene transfer in, 106 mechanism-based inactivators in, 210 457–458, 457f of immune system, 1049–1051 Michaelis-Menten, 203–207 erythropoietin receptor, 457–458, 457f in vitro, 1092–1094, 1095b–1096b, 1117b Michaelis-Menten equation for, 203, 203f erythrose, 246s introns in, 1088–1089 pH and, 210f, 212–213 erythrose 4-phosphate, in Calvin cycle, 806, Miller-Urey experiment in, 33–34, 33f rate equation for, 203, 203f 806f, 807f mitochondrial, 36, 37f rate measurement and, 207 erythrulose, 246s from endosymbiotic bacteria, 765–766 of regulatory enzymes, 227–228, 228f ES complex. See enzyme-substrate complex molecular, 104–108 steady-state, 202, 203–205 Escherichia coli. See also bacteria amino acid sequences and, 104–108, 106f–108f steady-state assumption and, 202 citric acid and glyoxylate cycles in, 658–659 amino acid substitutions in, 106 substrate concentration and, 201f, 203f cloning in, 314–325 homologs in, 106–107 reaction rate and, 201–203, 201f, 203f DNA in, 981, 982t, 1002–1003, 1003f horizontal gene transfer in, 106 for regulatory enzymes, 228, 228f packaging of, 1002–1003, 1003f of molecular parasites, 1094 suicide inactivators in, 210, 211b–212b topoisomerases and, 990 mutations in, 32–33, 32f, 37–38, 1194b–1195b transition-state, 27, 193, 195–197, 217 DNA replication in, 1015–1025, 1015f–1025f natural selection in, 33 enzyme-linked immunosorbent assay (ELISA), fatty acids in, 396t nucleic acids in, 33–34, 1092–1094 178f, 179, 932 synthesis of, 834–839 photosynthesis in, 35, 37f, 788–790, 791f

enzyme multiplicity, 900 FoF1 complexes of, 766 prebiotic, 33–34 enzyme-substrate complex, 192, 192f, 195–197 genetic map of, 1010f prokaryotic, 35–36, 36f active site in, 158, 192, 192f genome of, 981 protein families and, 140 binding energy of, 53, 53f, 54, 55f, inorganic polyphosphate in, 527 protein homologs in, 106–107 195–197 lac operon in, 1159–1160, 1159f proteins in, 1092–1094 rate acceleration and, 195–197 regulation of, 1165–1167, 1166f retrotransposons in, 1088–1089 specifi city and, 197–198 lactose transporter in, 416, 416f, 416t retroviruses in, 1088–1089 bisubstrate, 206–207, 207f lipopolysaccharides of, 268 RNA world hypothesis and, 34–35, 34f, dissociation constant for, 204 membrane proteins of, structure of, 393f 1093–1094 induced fi t in, 198, 219–220, 220f metabolism in, 28–29 time line of, 36–37, 36f lock-and-key confi guration in, 195–196, 195f metabolome of, 591, 591f transcription in, 1092–1094 ordered water and, 53, 53f as model organism, 4–5 evolutionary trees, 107–108, 108f substrate concentration in phospholipid synthesis in, 853–855, 854f excinucleases, 1032 reaction rate and, 201–203, 201f, 203f. See protein folding in, 147, 148f excited state, 771 also enzyme kinetics protein targeting in, 1145–1146, 1146f exciton, 771 in regulatory enzymes, 203f, 228, 228f recombinant gene expression in, 322, 322f exciton transfer, 771 in transition state, 195–197 ribosome of, 7f, 1115–1117, 1116f in photosynthesis, 774–775, 775f turnover number for, 205, 205t RNase P of, 295f exenatide (Byetta), 970t weak interactions in, 53, 53f, 54, 195–197, 196f signaling in, 473, 473f exergonic reactions, 24, 25, 27 epidermal growth factor receptor, 463 structure of, 4–6, 7f in citric acid cycle, 655 oncogenic mutations in, 489, 490b transcription in, 1058–1064, 1058f in conversion of pyruvate to phosphoenolpyruvate, epigenetics, 998b–999b Escherichia coli expression vector, 322, 322f 570–572, 570t, 571f, 572f epimers, 245, 246f Escherichia coli plasmid vector, 317–319, 318f, coupled with endergonic reactions, 24–25, 24f epinephrine, 438s, 909, 934 319f exit (E) binding, ribosomal, 1128 cascade mechanism of, 622f ESI MS, 101, 101f exocytosis, 8 in glucose metabolism, 958, 959t essential amino acids, 709, 892. See also amino exogenous pathways, 866 in lipid metabolism, 958, 959t acid(s) exome, 340b as neurotransmitter vs. hormone, 930 essential fatty acids, 845 exons, 343–344, 343f, 984, 1070 regulation of, 438–446, 439f esters transcription of, 1070 as signal amplifi er, 933 oxygen, free-energy hydrolysis of, 521–522, 522f exonuclease(s), 1013 synthetic analogs of, 439f standard free-energy changes of, 509t in mismatch repair, 1030, 1031f epinephrine cascade, 443–444, 444f estradiol, 372f, 372s, 475s, 935 exonuclease III, 315t epitope, 175 estrogens, 372, 372f, 372s, 475s, 935 expression vectors, 321–325 epitope tagging, 333–334, 335, 335f synthesis of, 874, 874f extracellular matrix, 260 equilibrium, 25 ETF:ubiquinone oxidoreductase, 739f, 740 glycosaminoglycans in, 260–262, 261f, 262f,

equilibrium constant (Keq), 25, 59, 194 ethane, 529s 264–266 for ATP hydrolysis, 511 ethanol. See alcohol(s) proteoglycan aggregates in, 266, 266f calculation of, 507–508, 511 from biomass, 816b–817b proteoglycans in, 263, 264–266, 266f in carbohydrate metabolism, 593, 593t ether lipids, 364, 365f extrinsic pathway, 233 free-energy change and, 194, 194t, 507–508, ethylene receptor, in plants, 475f 508t, 509t etoposide (Etopophos), 993b, 993s for two coupled reactions, 511 euchromatin, 998b, 1175 F for water ionization, 59 Eukarya, 4, 4f F-actin, 180f, 181 equilibrium expression, 160 eukaryotes, 3 in muscle contraction, 182

erbB2 oncogene, 489 cell structure in, 6–8, 7f F1-ATPase, 750 ergocalciferol (vitamin D2), 373, 373f evolution of, 36–37, 36f structure of, 760, 760f ERK, 455, 455f eukaryotic DNA, 981–983, 982t F1 component, of ATP synthase, 750, 751f erlotibin, 491b evaporation, 48t, 49 stabilization of ATP relative to ADP on, error-prone translesion DNA synthesis, evolution, 32–39 750–751, 751f 1034–1037, 1036t adaptation to aqueous environments in, 69–70 F-type ATPase, 412–413, 413f. See also ATP erythrocytes, 949, 950f adenine in, 1093 synthase(s) aquaporins of, 418–419, 419t amino acid sequences in, 104–108, 106f–108f Fab fragment, 175, 176f, 177f chloride-bicarbonate exchanger in, 398f, amino acid substitutions in, 106 Fabry disease, 369b 407–409, 407f of bacteria, 35–36, 36f, 788–790 facilitated diffusion, 403–404, 404f. See also culling of, 270 cellular specialization in, 36–37 transporter(s) formation of, 163 of chloroplasts, 788–789 factor VII, 234 G6PD-defi cient, Plasmodium falciparum divergent, 644 factor VIIa, 234 inhibition of, 576b of -oxidation enzymes, 683–684 factor VIII, defi ciency of, 234, 235f in glucose transport, 406f, 408f endosymbiosis in, 36, 37f, 765–766, 788–789 factor VIIIa, 233, 234 glucose transport in, 405–407, 405f, 406f eukaryotic, 36–37, 36f, 37f factor IX, 234 glycolytic reactions in, free-energy in Galapagos fi nches, 1194b–1195b factor IXa, 234 changes of, 570t genetic divergence in, 38 factor X, 234 BMInd.indd Page I-15 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-15

factor Xa, 234 yielding acetyl-CoA and ATP, 674–675, 676t ferrous ion, oxidation of, 528–529 factor XI, 234 complete, 677–678, 680b–681b fetus, hemoglobin-oxygen binding in, 172 FAD (fl avin adenine dinucleotide), 307s, 536s enzymes of, 669–672, 670f–672f fi brin, 233, 374 familial HDL defi ciency, 874 of monounsaturated fat, 677, 677f fi brinogen, 233, 374 familial hypercholesterolemia, 868, 871–873, odd-number, 677–678, 678f fi broblast growth factor, 262f, 265, 265f 872b–873b , 684–685, 685f fi broin, 130, 131f Fanconi-Bickel disease, 617t in endoplasmic reticulum, 684–685, 685f fi bronectin, proteoglycans and, 266, 266f Faraday constant, 410, 507t of polyunsaturated fats, 677, 678f fi brous proteins, 125–130 farnesyl groups, membrane attachment of, 394f regulation of, 678–679 coiled coils in, 126, 126f farnesyl pyrophosphate, 861 stages of, 673f collagen as, 127–130, 127f in cholesterol synthesis, 862f of unsaturated fats, 677, 677f, 678f fi broin as, 130, 131f farnesylation, of amino acid residues, 1136, 1137f fatty acid synthase, 834–839 in hair, 126, 126f, 127b Fas receptor, in apoptosis, 493, 494f active sites of, 834–836 -keratin as, 126–127 fast-twitch muscle, 944 associated proteins of, 836–838 polypeptide chain arrangement in, 125 fasting state, glucose metabolism in, 955–956, 955f, in plants, 839 structure of, 126f, 127–130, 127f 957f, 958f variants of, 834, 835f functional correlates of, 126t fat(s) fatty acid synthesis, 943–944 secondary, 120–125, 120f, 122f–124f, 126t body. See also adipose tissue; body mass acetoacetyl-ACP in, 837f, 838 tertiary, 96f, 97, 125–140, 127f, 130f, 131f. heat generated by, in oxidative acetyl-CoA carboxylase in, 833, 834f, See also tertiary protein structure phosphorylation regulation, 762–763, 763f 841, 842f fi ght-or-fl ight response, epinephrine in, 958, 959t metabolic pathways of, 942t acetyl-CoA in, 833, 834f, 838–839, 951–952 fi laments, cytoskeletal, 8–9, 8f rancid, 361 acetyl-CoA–ACP transacetylase in, 837f Fire, Andrew, 1185, 1185f fat cells. See adipocytes acyl carrier protein in, 836, 836f, 837f fi refl y bioluminescence cycle, 525b fat-STATs, 963 adipose tissue in, 943–944 fi rst law of thermodynamics, 21 fatty acid(s), 357–362. See also lipid(s); in bacteria, 834–839, 843 Fischer, Emil, 78, 195 triacylglycerol(s) trans-⌬2-butenoyl-ACP in, 837f, 838 Fischer projection formulas, 244, 245f, 247–248 activation and transport of, 670–672, 671f butyryl-ACP in, 837f, 838 5Ј cap, 1070 as amphipathic compounds, 52–53, 52f carbonyl group reduction in, 837f, 838–839 5Ј end, 285, 305f analysis of, 377f, 378 condensation in, 837f, 838 5Јn3Ј exonuclease activity, in DNA polymerases, body stores of, 956t in cytosol, 839, 840f 1017, 1017f desaturation of, 842–845, 842f, 843f dehydration in, 837f, 838 fi xation, in nitrogen cycle, 882 double bonds of, 357–358, 358t in diabetes mellitus, 849–850 fl agella, 6f in E. coli cells, 396t double-bond reduction in, 837f, 838 fl agellar motion, 179 essential, 845 in endoplasmic reticulum, 840f, 842, 843 fl avin adenine dinucleotide (FAD), 307s, 536s free, 359–360, 669 enoyl-ACP reductase in, 837f, 838 fl avin mononucleotide (FMN), 536f in glycerophospholipids, 363–365 fatty acid synthase in, 834–839 fl avin nucleotides, 535–537, 536t, 734–735 as hydrocarbon derivatives, 357 fatty acyl chain elongation in, 834, 842, 851f fl avoproteins, 89t, 535–537, 536f, 536t, 734–735 as lipid anchors, 394, 394f in hepatocytes, 843 electron-transferring, 674 lysosomal degradation of, 368, 368f -hydroxyacyl-ACP dehydratase in, 837f, 838 fl ickering clusters, 48, 52f melting point of, 358t, 359 insulin in, 951–952 fl ip-fl op diffusion, of membrane lipids, mobilization of, 849–850, 850f, 943–944 -ketoacyl-ACP reductase in, 837f, 838 396–397, 396f glucagon in, 955–956 -ketoacyl-ACP synthase in, 837f, 838 fl ippases, 396f, 397 nomenclature for, 357–359, 357f, 358t malonyl/acetyl-CoA–ACP transacetylase in, 838 fl oppases, 396f, 397 omega-3, 359 malonyl/acetyl-CoA–ACP transferase in, 837f fl uid mosaic model, 387, 387f omega-6, 359 malonyl-CoA in, 842 fl uorescence, 771 packing of, 359, 359f malonyl-CoA–ACP transferase in, 837f fl uorescent resonance energy transfer (FRET), physical properties of, 358t, 359–360 palmitate in, 834, 837f, 842, 842f 448b–449b polyunsaturated, 359 palmitate synthesis in, 811f, 834, 838–839 L-fl uoroalanine, 907 reesterifi cation of, 849–850 in plants, 839, 840f fl uoroquinolones, 992b–993b saturation of, 361, 361f regulation of, 840–842, 842f, 849–850 fl uorouracil, 923, 924f in signaling, 847 steps in, 834, 837f, 838 fl ux (J ), 589, 597, 598b–599b solubility of, 358t, 359 in vertebrates, 842f enzymes contributing to, 596–597 structure of, 357–359, 358t in yeast, 842f glycolytic, 596f synthesis of, 833–845 fatty acyl–CoA, 670–671 increased, metabolic control analysis prediction trans, 361, 362t conversion of fatty acids into, 670–671, 671f of, 598b–599b in triacylglycerols, 359f, 360–361, 360f, 361f. See in triacylglycerol synthesis, 848–849, 848f metabolite, change in enzyme activity on, 596f, also triacylglycerol(s) fatty acyl–CoA dehydrogenase, genetic 597, 597f fatty acid catabolism, 667–688 defects in, 682 response coeffi cient effect on, 598b–599b digestion, mobilization, and transport in, 668–672 fatty acyl–CoA desaturase, 843 fl ux control coeffi cient (C), 597, 597b ketone bodies in, 686–688 fatty acyl–CoA synthetase, reaction mechanism of, fMet-tRNA, in protein synthesis, 1127 oxidation in, 672–686. See also fatty acid 670–671 posttranslational modifi cation of, 1136 oxidation Fc region, 175, 176f, 177f FMN (fl avin mononucleotide), 536f

fatty acid metabolism Fe-S reaction center, 777. See also iron-sulfur Fo component, of ATP synthase, 750 in adipose tissue, 849–850, 850–852, 851f, 936f, entries rotation of, 752–755, 755f, 756f 943–944, 957f, 958f feedback inhibition, 29 foam cells, 871, 872f

in brain, 949 in purine nucleotide biosynthesis, 914–915, 914f FoF1 complex, of Escherichia coli, 766 cortisol in, 958–959 in pyrimidine nucleotide biosynthesis, 916, 916f folate defi ciency, 713–714, 920 in diabetes mellitus, 559f sequential, 900 folate metabolism, as chemotherapy target, 924f epinephrine in, 958, 959t Fehling’s reaction, 250b folds, 133–140, 137, 139f–140f. See also protein in fasting/starvation, 957f, 958f FeMo cofactor, 883 folding in liver, 942, 943f fermentation, 544, 565, 565, 566b food in muscle, 944–948, 945f in beer brewing, 565, 566b from fermentation, 566–568 pathways of, 942t ethanol (alcohol), 544, 548f, 565, 565f trans fatty acids in, 361, 362t fatty acid oxidation, 667, 672–686 foods produced by, 566–568 footprinting, 1062b , 685–686 industrial-scale, 566–568 Forbes disease, 617t in peroxisomes, 685f lactic acid, 546 forensic medicine, DNA genotyping in, 329–330 pyruvate in, 563–565 forkhead box other (FOXO1), 610, 610f in bears, 676b thiamine pyrophosphate in, 565, 567f, 568t formaldehyde, 529s enzymes of, 683–684, 684f ferredoxin, 778, 780, 886 formic acid, 529s in peroxisomes, 682–683, 683f ferredoxin-thioredoxin reductase, 811–812, 811f N-formylmethionyl-tRNAf Met, in protein in plants, 683, 683f ferredoxin:NADPϩ oxidoreductase, 781 synthesis, 1127 steps in, 673–675, 673f ferritin, 642b posttranslational modifi cation of, 1136 BMInd.indd Page I-16 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-16 Index

454 sequencing, 339–341, 341f functional genomics, 38–39 GDGT (glycerol dialkyl glycerol tetraether), FOXO1 (forkhead box other), 610, 610f functional groups, 12–14, 13f, 14f 365, 367f fraction, 89 furanoses, 247, 247f, 248f GDP (guanosine 5Ј-diphosphate) fractionation fused gene, 334 in -adrenergic pathway, 438, 439f cellular, 8, 8f, 57 fushi tarazu, 1190, 1190f in olfaction, 481, 482f protein, 89–90, 90f fusion proteins, 325, 333, 400 in vision, 478–479, 479f frameshifting, 1111 futile cycles, 601, 850 gel electrophoresis. See electrophoresis Framingham Heart Study, 872 triacylglycerol cycle as, 850 gene(s), 281, 979–980. See also protein(s) Franklin, Rosalind, 288, 288f bacterial, 984 FRAP technique, 397f, 398 mapping of, 1010f free energy (G), 25, 506 G naming conventions for, 1010 cell sources of, 507 G (free energy). See free energy (G) caretaker, 492 enthalpy and, 23 G-actin, 180f, 181 chromosome population of, 981 entropy and, 23 G protein(s), 441b–443b cloned. See also cloning Gibbs, 506 binary switches in, 438, 440f, 441b–443b alteration of, 323–325, 325f of hydrolysis, 517–519, 520f, 521–522, 521f, disease-causing defects in, 442b–443b expression of, 321–325, 322f

521t, 522f Gi (inhibitory), 446 defi nition of, 281, 979–980, 980 free-energy change (⌬G), 25–26, 192, 193f, 506 Golf, 481, 482f evolutionary divergence of, 38 in ATP hydrolysis, 518–519, 518f, 520f Gq, 447 exons in, 984, 1070 calculation of, using standard reduction Gs (stimulatory), 438, 439f transcription of, 1070 potential, 531–532 adenylyl cyclase and, 438 functional analysis of, 333–337. See also protein in carbohydrate metabolism, 593t self-inactivation of, 438 function of electrochemical gradient, equation for, 744 Ras-type, 441b, 455, 456f functional classifi cation of, 38–39 in enzymatic reactions, 25, 192–193, 193f, 194, in signaling, 437–452 functionally related, identifi cation of, 334–337 194t, 197–198 small, 455 fused, 334 of esterifi cation, 509t Ras-type, 441b, 455, 456f gap, 1188, 1190 of glycolytic reactions in erythrocytes, 570t in signaling, 455 homeotic, 1188, 1190–1191, 1191f, 1192f in membrane transport, 409–410 stimulatory, 438 homologous, 38 vs. standard free-energy change, 509. See also trimeric, 438 housekeeping, 1156 standard free-energy change G protein–coupled receptor(s) (GPCRs), 436f, 437, immunoglobulin, recombination of, 1049–1051, free fatty acids (FFAs), 359–360, 669. See also 438–446, 482–484, 483f, 483t 1051f, 1052f fatty acid(s) -adrenergic receptor as prototype of, 438–446 introns in. See introns free-living bacteria, nitrogen-fi xing, 887–888 evolutionary signifi cance of, 482–483 jumping, 1039, 1049 free radicals, 514–515, 515f heptahelical, 438 maternal, 1188, 1188–1190, 1189f FRET (fl uorescent resonance energy transfer), G protein–coupled receptor kinases (GRKs), 446 mutation of. See mutations 448b–449b G tetraplex, 292 naming conventions for, 1010 fructokinase, 561 GABA (-aminobutyric acid), 909 number in genome, 342 fructose, 243, 244s, 245, 246s receptor for, as ion channel, 424 orthologous, 38, 333 fructose 1,6-bisphosphatase, 572–573 gag, 1086f, 1087 pair-rule, 1188 light activation of, 811, 811f frameshifting and, 1111 paralogous, 38, 333 fructose 1,6-bisphosphate, 549, 549s gag-pol, frameshifting and, 1111 pattern-regulating, 1188–1191 in Calvin cycle, 806, 806f GAL genes, regulation of, 1181 reporter, 334 cleavage of, 550, 551f Gal4p segment polarity, 1188, 1190 conversion to fructose 6-phosphate in acidic activation domain of, 1181 segmentation, 1188 gluconeogenesis, 570t, 572–573 in yeast two-hybrid analysis, 335–337 size of, 980, 981t in glycolysis, 544, 545f D-galactitol, 562s stability, 492 phosphorylation of fructose 6-phosphate to, galactokinase, 562 gene expression 549–550 galactolipids, 365, 365f of cloned genes, 321–325, 322f, 325f regulation of, 604, 605f galactosamine, 249–250, 249s constitutive, 1156 fructose 1,6-bisphosphate aldolase, 550 galactose, 245, 246s induction of, 1156 fructose 2,6-bisphosphatase (FBPase), conversion of, to glucose 1-phosphate, 571f recombinant, in bacteria, 322, 322f 604, 605f, 606 epimers of, 246s regulated, 1156. See also gene regulation fructose 2,6-bisphosphate (F26BP), 605, 605s, oxidation of, 249f, 250 repression of, 1156 820, 820f galactose metabolism genes, regulation of, gene products in regulation of glycolysis and gluconeogenesis, 1180–1182, 1180f inducible, 1156 605–606, 605f galactosemia, 562 repressible, 1156 in sucrose synthesis, 820, 820f -galactosides, lac operon and, 1159–1160 gene regulation, 1155–1195 fructose 1-phosphate, 562s Galápagos fi nches, beak evolution in, acidic activation domain in, 1181 fructose 1-phosphate aldolase, 562 1194b–1195b activators in, 1157 fructose 6-phosphate, 549, 549s chains, immunoglobulin, 176 antigenic variation in, 1174t in Calvin cycle, 806, 806f, 807f ganglioside(s), 268, 366–367, 367f, 368f, 857 catabolite repression in, 1165 conversion of fructose 1,6-bisphosphate to, in functions of, 367–368 chromatin in, 1175–1176 gluconeogenesis, 570t, 572–573 lysosomal degradation of, 368, 368f coactivators in, 1178 conversion of glucose 6-phosphate to, 549, 549f structure of, 366s combinatorial control in, 1158–1159, 1177, 1177f phosphorylation to fructose 1,6-bisphosphate, synthesis of, 857 in development, 1186–1191 549–550 ganglioside GM2, 367f gene silencing in, 1185–1186, 1185f in sucrose synthesis, 820, 825f, 826 in Tay-Sachs disease, 369b DNA-binding domains in, 1160–1163, -D-fructofuranose, 247 gangliosidosis, 369b 1162f–1164f fruit fl y gap genes, 1188, 1190 effectors in, 1157 development in GAPs (GTPase activator proteins), 442b enhancers in, 1178 gene regulation in, 1186–1191 gas constant (R), 507t in eukaryotes, 1176–1195 pattern-regulating genes in, 1188–1191 gas-liquid chromatography, 378 steps in, 1179–1180 genome of, 981, 982t gases, solubility of, 51, 51t in glucose metabolism, 608–609, 609t life cycle of, 1186–1187, 1186f gastric enzymes, 697, 698f histone in, 1175–1176 ftz, 1190, 1190f gastric ulcers, 271f, 272 hormonal, 471–472, 1182–1184, 1183f fucose, 249s gastrin, 697 host range, 1174t fumarase, 647 gastrointestinal tract, 698f induction in, 1156, 1160 fumarate, 646 GATC sequences insulin in, 453–457, 456f, 624, 1184 glucogenic amino acids and, 574t in mismatch repair, 1029, 1029f, 1030, 1030f mating-type switch in, 1174t oxidation of succinate to, 646–647 in replication, 1020 mRNA in, 1171–1173 fumarate hydratase, 647 Gaucher disease, 369b negative, 1157, 1158f fumaric acid, 16–17, 16f, 16s GCN5-ADA2-ADA3, 1176t operators in, 1157 BMInd.indd Page I-17 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-17

operons in, 1159–1160 DNA sequences in, 342–345, 343f, 344f kinetic properties of, 603, 603f regulation of, 1165–1167, 1166f eukaryotic, 981–983, 982t regulation of, 603–604, 603f phase variation in, 1173, 1173f evolution of, 37–38, 345–347 gluconate, 249s positive, 1157, 1158f, 1176–1177 mapping of. See genome sequencing gluconeogenesis, 568, 568–575, 601. See also in eukaryotes, 1176–1177 number of genes in, 342 glucose metabolism principles of, 1156–1165 synteny in, 333 amino acids in, 574, 574t, 942 in prokaryotes, 1165–1174 viral, 980–981, 982t bypass reactions in proline-rich activation domains in, 1182 yeast, 981, 982t fructose 1,6-bisphosphate to fructose protein-protein interaction domains in, genome sequencing, 37–38, 38t, 333, 339–351 6-phosphate conversion, 570t, 572–573 1163–1165 in database construction, 333 glucose 6-phosphate to glucose conversion, recombinational, 1173–1174, 1174t databases for, 342, 348–349 570t, 573 regulons in, 1166 evolution and, 345–347, 346f, 349–350, 349f, 350f pyruvate to phosphoenolpyruvate conversion, repression in, 1156 454 sequencing in, 339–341, 341f 570–572, 570t, 571f, 572f repressors in, 1061, 1157, 1162, 1180 medical applications of carbohydrate synthesis and, 568–570, 569f translational, 1170–1171, 1184–1185, 1188 in disease gene identifi cation, 347–349, 348f in chloroplast, 820–821, 820f riboswitches in, 1172 in personalized genomic medicine, 39, 340b, citric acid cycle and, 574, 957–958, 957f RNA interference in, 1185–1186, 1185f 350–351 in fasting/starvation state, 956–958, 957f second messengers in, 1171 pyrosequencing in, 339–341, 341f in germinating seeds, 825–826 signaling in, 1171, 1182–1184 reversible terminator sequencing in, glycolysis and. See also glycolysis site-specifi c recombination in, 1038, 1046–1049, 341–342, 342f fructose 2,6-bisphosphate in, 605–606, 605f 1047f shotgun sequencing in, 341–342 opposing pathways of, 569–570, 569f, 601f SOS response in, 1035, 1036t, 1169–1170, 1169f for Neanderthals, 350b–351b regulation of, 574, 601–612 specifi city factors in, 1157 next-generation, 304, 339–342, 341f, 342f liver in, 940–941, 955–956, 956t, 957f stringent factor in, 1171, 1171f polymerase chain reaction in, 327–331 in muscle, 943–944, 948, 948f stringent response in, 1171, 1171f purposes of, 345–347 regulation of, 601–612, 605f, 607f, 850–852 TATA-binding protein in, 1177–1178, 1179 shotgun, 341–342 glycolysis and, 601–612 transcription activators in, 1178, 1181–1182 genomic databases, 342, 348–349 sequential reactions in, 573t transcriptional attenuation in, 1166f–1168f, genomic library, 332 in well-fed state, 951, 952f 1167–1169 genomic mapping, for E. coli, 1010f glucono--lactone, 249s translational repression in, 1170–1171, 1170f, genomics, 15, 39, 313, 339–351 Glucophage (metformin), 970t 1180, 1188 comparative, 39, 333, 345–348, 345f glucopyranose, 247f, 248f translational repressor in, 1170–1171 functional, 38–39 glucosamine, 249–250, 249s upstream activator sequences in, 1178 geometric isomers, 16–17 glucose, 244s, 549s in yeast, 1180f, 1181 geranyl pyrophosphate, 861 form of, 246, 247f gene silencing, by RNA interference, 1185–1186, in cholesterol synthesis, 860f, 862f form of, 246, 247f 1185f geranylgeranyl groups, membrane attachment of, blood levels of, 950 gene transfer, lateral, 106 394, 394f in diabetes, 960 general acid-base catalysis, 199, 199f germination, seed, triacylglycerols in, 683, 683f reference ranges for, 956t general recombination. See homologous genetic ghrelin, 962f, 966–967, 967f regulation of, 940–941, 941f, 951–960.

recombination Gi (inhibitory G protein), 446 See also glucose metabolism general transcription factors, 1066, 1066t, 1067f Gibbs, J. Willard, 23 blood tests for, 250b–251b genetic code, 1103–1113 Gibbs free energy (G), 506. See also free body stores of, 956t base composition in, 1105 energy (G) in cellulose synthesis, 822–823 base sequences in, 1105 Gilbert, Walter, 302 conversion of amino acids to, 711, 711f codons in, 1104f, 1105 Gilman, Alfred G., 441b, 441f conversion of glucose 6-phosphate to, in cracking of, 1104–1108 Gla, 234 gluconeogenesis, 570t, 573 degeneracy of, 1107, 1107t Gleevec, 491b degradation of. See glycolysis expansion of, 1124b–1126b glimepiride (Amaryl), 970t anaerobic. See fermentation overlapping, 1104f glipizide (Glucotrol), 970t epimers of, 246s reading frames in, 1067f, 1105 global warming, 816b–817b hexokinase catalysis of, 219–220, 220f second, 1122–1123 globins, 159, 159f. See also hemoglobin; myoglobin lac operon and, 1165–1167, 1166f triplet (nonoverlapping), 1104f, 1105 structure of, 141 membrane transport of. See glucose universality of, 1104f, 1107t, 1108 nuclear magnetic resonance studies of, transporters variations in, 1108b–1109b, 1134b 135b–136b, 135f, 136f in muscle contraction, 945f, 946–948, 948f wobble and, 1110 x-ray diffraction studies of, 134b–135b, in myocytes, control of glycogen synthesis from, genetic counseling, for inborn errors of metabolism, 134f–135f 598–600 369b globosides, 366, 367f oxidation of. See glucose oxidation genetic defects globular proteins, 125, 130–138 phosphorylation of, 251, 548–550 in amino acid catabolism, 717t, 718–721, 720f turns in, 123, 124f as reducing sugar, 251, 252 in fatty acyl–CoA dehydrogenase, 682, 692 diversity of, 130–131 regulation of, 940–941, 941f, 951–960. See also in urea cycle, 709–710 folding of, 130–131, 130–138, 132f glucose metabolism treatment of, 710f functions of, 130–131, 130–138 in starch synthesis, 818–819 genetic diseases hydrophobic interactions in, 132, 132f storage of, 951–953, 952f genetic counseling for, 369b in large proteins, 133–140, 137f, 138f in glycogen, 253, 255–256, 951–953, 952f inborn errors of metabolism in, 369b myoglobin as, 131–133, 132f, 133f in starch, 253, 255 linkage analysis for, 347–349, 348f polypeptide chain arrangement in, 125 structure of, 10s, 219, 219s, 244, 245, 246s protein misfolding in, 148–151 small, structure of, 130–138 synthesis of, 942 genetic engineering, 314. See also cloning; in small proteins, 130–138, 133t triacylglycerol conversion to, 683, 683f recombinant DNA technology structure of, 130–131, 130–138, 132f UDP. See UDP-glucose genetic map, of E. coli, 1010f glomerular fi ltration rate (GFR), 947b urine tests for, 250b–251b genetic mutations. See mutations glucagon, 605, 951, 953, 955–956 utilization of, 543 genetic recombination. See also DNA recombination cascade mechanism of, 622f glucose-alanine cycle, 703, 703f, 942 functions of, 1039 in cholesterol regulation, 870, 870f glucose carbon, in formation of glyceraldehyde homologous, 1038–1043 in fatty acid mobilization, 956 3-phosphate, 552f site-specifi c, 1038, 1046–1049, 1047f, 1048f in glucose metabolism, 955–956 glucose catabolism, 942t genetics, overview of, 29–32 in glucose regulation, 955f in cancerous tissue, 555, 556b–557b genome, 3, 15, 37 glucocorticoids, 372, 372f, 372s, 933t, 935. glucose metabolism, 951–960 annotated, 38 See also under steroid in adipose tissue, 943–944, 943f bacterial, 981, 982t synthesis of, 874, 874f, 875f in brain, 949, 949f chimpanzee vs. human genome, 345–347, 345f glucogenic amino acid, 711 cortisol in, 958–959 components of, 984 glucokinase, 617, 940 in diabetes mellitus, 558, 559f, 959–960 contents of, 342–345, 344f in glucose regulation, 953f, 954 epinephrine in, 958, 959t BMInd.indd Page I-18 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-18 Index

in fasting state, 955f, 956–958, 957f, 958f glutaminase, 703 as precursor of porphyrins, 902–904, 905f glucagon in, 955–956 glutamine, 79s, 81, 696, 709, 710s, 721, 888, properties of, 77t insulin in, 951–953, 952f, 952t 892, 923f receptor for, as ion channel, 424 in liver, 940–941, 941f, 952f, 955–956, 956t ammonia transported in bloodstream as, in secondary structures, 124, 124f in muscle, 945f, 946–948, 948f 702–703, 702f titration curve for, 82–84, 83f neuronal, 949, 949f biosynthetic pathway of, 888–890 glycine cleavage enzyme, 715, 894 pancreas in, 952t, 953–955, 953f catabolic pathways for, 721f reaction mechanism of, 715f in starvation, 956–958, 957f, 958f in nitrogen metabolism, 696 glycine decarboxylase complex, 806f, 813f, 814 in well-fed state, 951–953, 952f properties of, 77t, 81 glycine synthase, 849 glucose oxidation, 26, 249f, 250 glutamine aminotransferase, 890–891, 890f glycobiology, 269 ATP yield from, 760t proposed reaction mechanism for, 910f glycoconjugates, 243, 263–268, 263f cellular, to carbon dioxide, 532 glutamine-rich domains, 1182 glycolipids, 263, 268, 268f energy-coupled reactions in, 24f, 26 glutamine synthetase, 235, 702, 888 glycoproteins, 263–264, 263f, 266–268, 268f neuronal, 949, 949f allosteric regulation of, 889–890, 889f proteoglycans, 263–268, 263f, 264f pentose phosphate pathway of, 577f. See also in nitrogen metabolism, 889–890 glycogen, 244, 255–259, 262t. See also pentose phosphate pathway reaction of, 888 polysaccharide(s) glucose 1-phosphate, 617 subunit structure of, 889 biosynthesis of, in bacteria, 819 conversion of galactose to, 571f glutaredoxin, 917 body stores of, 956t glycolysis of, 614–615, 614f, 616b, 617t glutathione, 906–907 branch synthesis of, 619f in starch synthesis, 819 amino acids as precursors of, 906–907 degradation of, glycogen phosphorylase in, 569f, -D-glucose 1-phosphate, 613–614, 613f biosynthesis of, 908f 613–614, 613f, 615f glucose 6-phosphatase, 573 in cell protection against oxygen derivatives, glucose removal from, 256 hepatic metabolism of, 940–941, 941f 576b, 576f glucose storage in, 253, 255–256 hydrolysis of glucose 6-phosphate by, metabolism of, 908f glycogenin priming of sugar residues in, 619, 614–615, 615f glutathione peroxidase, 745, 907 619f glucose 6-phosphate, 219s, 249f, 251, 548, 587, glutathione-S-transferase tag, 326, 326f granular form of, 256 593t, 617, 941f GLUTs. See glucose transporters in hepatocytes, 256 conversion of glyburide, 970t hydrolysis of, 256 to fructose 6-phosphate, 549, 549f glycans, 254. See also polysaccharide(s) metabolism of, 612–620 to glucose in gluconeogenesis, 570t, 573 glycated hemoglobin, 250b–251b glucose 1-phosphate in, 614–615, 614f fate of, 940–941, 941f glyceraldehyde, 244, 246s, 562s glycogen breakdown in, 613–614, 614f, 673f in glycolysis, 580, 580f isomers of, 244–245, 245f glycogenin in, 619, 619f, 634f hepatic metabolism of, 940–941, 941f glyceraldehyde 3-phosphate, 550, 550s phosphoprotein phosphatase 1 in, 624, 625f hexokinase catalysis of, 219–220 catalysis of, 198 sugar nucleotide UDP-glucose in, 618f, 619f hydrolysis of, by glucose 6-phosphatase, in Calvin cycle, 805, 806f, 807f UDP-glucose in, 615–619 614–615, 615f glucose carbons in formation of, 552f in muscle, 945f, 946–948, 948f insulin regulation of, 951–953 in glycolysis, 545f, 546 reducing end of, 256 nonoxidative recycling of pentose phosphates to, oxidation to 1,3-bisphosphoglycerate, 551–552, storage of, 613, 613f 577–580, 578f, 579f, 580f 553f structure of, 255–256, 256f, 258, 260f, 262t in pentose phosphate pathway, 580, 580f, synthesis of, 804–805, 808f, 809, 824f synthesis of, 456, 456f, 618f 940–941 glyceraldehyde 3-phosphate dehydrogenase, 534t, control vs. regulation of, 598–600 glucose 6-phosphate dehydrogenase (G6PD), 534t, 551, 593t, 804, 805f, 808–809 regulation of, 601–612 575–576 light activation of, 811–812, 811f sugar nucleotides in, 615–619 defi ciency of, 576b reaction mechanism of, 552, 553f glycogen granules, in hepatocyte, 613, 613f light inactivation of, 812 glycerol, 360s glycogen phosphorylase, 230, 560, 951 glucose tolerance test, 960 in archaeal membrane lipids, a/b forms of, 230, 621 glucose transporters, 626; See also specifi c GLUT 365–366, 366f allosteric modifi cation of, 235 transporters chiral forms of, 363, 363f covalent modifi cation of, 230f in diabetes, 408b, 558, 559f in galactolipids, 365f glycogen breakdown by, 230, 235, 569f, 613–614, erythrocyte (GLUT1), 405–407, 405f, 406f, 407t in phospholipids, 363–365, 363f, 364f 613f, 614f intestinal (GLUT2), 406–407, 407t, 416–417, structure of, 360s, 363s interconvertible forms of, 621 417f, 953–954 in triacylglycerols, 359f, 360–361, 360f, 848f phosphorylation of, 230 muscle (GLUT4), 407t, 408b, 456, 456f glycerol dialkyl glycerol tetraethers (GDGTs), regulation of, 230, 620–622 in diabetes, 408b 365, 367f allosteric and hormonal, 623f, 624f Naϩ-glucose symporter, 417, 417f glycerol kinase, 670, 848, 848f glycogen storage diseases, 616b–617b, 617t types of, 407t glycerol 3-phosphate glycogen synthase, 231, 456, 456f, 618, 951 glucosuria, 959 in carbohydrate synthesis, 826, 826f phosphorylation of, 230 glucosylcerebroside, 367f in glyceroneogenesis, 850 primer for, 619 Glucotrol (glipizide), 970t in lipid synthesis, 848, 848f, 850, 854f regulation of, 623–624, 623f, 624f glucuronate, 249f, 249s, 261, 261s synthesis of, 850, 850f, 851f glycogen synthase a, 623 GLUT1 transporter, 405–407, 405f, 406f, 407t, 416 glycerol 3-phosphate dehydrogenase, 740, glycogen synthase b, 623–624 GLUT2 transporter, 406–407, 407t, 417f, 418, 603, 848, 848f glycogen synthase kinase 3 (GSK3), 456, 456f, 603f, 953–954 glycerol 3-phosphate shuttle, 759, 759f 461–462, 461f, 623 GLUT4 transporter, 407t, 408b, 456, 456f glyceroneogenesis, 574, 850–852, 851f. See also effects of, on glycogen synthase activity, in diabetes, 408b glucose metabolism 623, 623f glutamate, 79s, 81, 721, 888, 892 glycerophospholipid(s), 362–363, 363–365, 363f, insulin activation of, 623, 624, 624f ammonia released by, 700–702, 702f 364f, 367f. See also triacylglycerol(s) glycogen-targeting proteins, 624 biosynthesis of proline and arginine from, 892, fatty acids in, 363–364 glycogenesis, 613 893f head groups of, 363, 852–853, 854f, 855, 857 glycogenin, 619 biosynthetic pathway of, 888 nomenclature of, 363, 364f and glycogen particle, 620f catabolic pathways for, 721f structure of, 363, 363s as primer for glycogen synthesis, 619, 620f in nitrogen metabolism, 696 synthesis of, 848–849, 848f structure of, 619, 619f properties of, 77t, 81 head group attachment in, 852–853, 854f sugar residues in glycogen and, 619 titration curve for, 85, 85f transport of, 857–858 glycogenolysis, 613 L-glutamate dehydrogenase, 534t, glycine, 79, 79s, 715, 894 glycolate pathway, 813–815, 813f 700–701 in helix, 122, 124, 124f glycolipids, 268, 268f, 363. See also lipid(s) oxidative deamination catalyzed by, biosynthesis of, 892–894, 894f neutral, 363f, 366, 367f 700–701, 702f as buffer, 84, 84f synthesis of, 857, 859f glutamate-oxaloacetate transaminase (GOT), in collagen, 127, 127f transport of, 857–858 708, 708b degradation of, to pyruvate, 715–717, 715f, 716f glycolysis, 544–558, 671f, 951–953, 952f. See also glutamate-pyruvate transaminase (GPT), 708b in photosynthesis, 806f, 813f, 814 glucose metabolism

glutamate synthase, 888 pKa of, 83–84, 84f ATP formation coupled to, 546 BMInd.indd Page I-19 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-19

in chloroplast, 820f glyoxylate cycle, 657–659, 657f–659f gulose, 246s in diabetes mellitus, 558, 559f four-carbon compound production from, 657–658 gustation, signaling in, 481, 483f, 484f feeder pathways for, 558–563, 569f in plants, 825, 825f, 826 gustducin, 481 glycogen and starch degradation in, 560–561 regulation of citric acid cycle and, 658–659, gut bacteria, obesity and, 968 monosaccharides in, 561–563, 571f 680f–681f polysaccharide and disaccharide hydrolysis in, glyoxysomes, 826, 826f 558–560 oxidation in, 683f H free-energy changes of, in erythrocytes, 570t in plants, 683, 683f Hϩ. See hydrogen ion(s) gluconeogenesis and. See also gluconeogenesis glypicans, 264, 264f H (enthalpy), 23, 506

fructose 2,6-bisphosphate in, 605–606, 605f GMP (guanosine 5Ј-monophosphate), 283s, H4 folate (tetrahydrofolate), 712, 712f opposing pathways of, 568–570, 569–570, 308, 308s conversions of one-carbon units by, 712f 569f, 601f Goldberger, Joseph, 535 substrate binding to, 195f regulation of, 574, 601–612 Goldstein, Joseph, 868, 868f, 873b hair

of glucose 1-phosphate, 614–615, 614f, Golf, 481, 482f coiled coils in, 126f 616b–617b, 617t Golgi complex, 6, 7f -keratin in, 126–127 glucose 6-phosphate in, 579f, 580, 580f lectins and, 269–273 permanent waving of, 127b payoff phase of, 545f, 546 protein sorting in, 1142 hairpin loops ATP and NADH in, 550–555, 553f transport vesicles of. See transport vesicles in DNA, 292, 292f, 999, 1000f conversion of 3-phosphoglycerate to GOT (glutamate-oxaloacetate transaminase), 708b in replication fork, 1012, 1012f 2-phosphoglycerate in, 554, 554f gout, 922–923 in RNA, 295, 295f, 1065f, 1084–1085 dehydration of 2-phosphoglycerate to GPCRs. See G protein–coupled receptors Haldane, J. B. S., 68b, 190, 190f, 196, 202 phosphoenolpyruvate in, 554 G6PD. See glucose 6-phosphate dehydrogenase half-reaction, 528–529 oxidation of glyceraldehyde 3-phosphate to (G6PD) standard reduction potentials of, 531t 1,3-bisphosphoglycerate in, 551–552, 553f GPI-anchored proteins, 394, 394f, 399 Halobacterium salinarum, 789–790

phosphoryl transfer from Gq, 447 bacteriorhodopsin in, 391, 391f 1,3-bisphosphoglycerate to ADP in, 552–554 grana, 770 halophilic bacteria, ATP synthesis in, phosphoryl transfer from phosphoenolpyru- Grb2, 454, 456f, 457 789–790, 791f vate to ADP in, 554–555 SH2 domain of, 454, 456f hammerhead ribozyme, 1082, 1082f, 1083 phosphorylated hexoses in, 546–548 green-anomalous trichromats, 480 Hanson, Richard, 850 preparatory phase of, 544–546, 545f, 548–550 greenϪ dichromats, 480 haplotypes, 344–345, 345f ATP in, 549f, 551f, 552f green fl uorescent protein (GFP), 333, 334, 334f, haptens, 175 cleavage of fructose 1,6-bisphosphate in, 335f, 448b–449b Harden, Arthur, 548, 548f 550, 551f greenhouse effect, 816b–817b Hartley, B. S., 215 conversion of glucose 6-phosphate to fructose GRK2, 445 HAT (histone acetyltransferases), 1176 6-phosphate in, 549, 549f GRKs (G protein–coupled receptor kinases), 446 Hatch, Marshall, 816 glycogen, starch, disaccharides, and hexoses GroEL/GroES, in protein folding, 147, 148f Haworth perspective formulas, 247–248, 248f in, 569f ground state, 192, 771 HDLs. See high-density lipoproteins (HDLs) interconversion of triose phosphates in, 550, ground substance. See extracellular matrix head group exchange reaction, in phospholipid 552f group transfer reactions, 515–516 synthesis, 855–856 phosphorylation of fructose 6-phosphate to growth factors, 487, 487f heart attack, 708, 948 fructose 1,6-bisphosphate in, 549–550 Grunberg-Manago, Marianne, 1085, 1085f heart disease

phosphorylation of glucose in, 549 Gs, 438 angina in, nitrovasodilators for, 440 regulation of, 555, 849–850 GSH. See glutathione atherosclerotic, 871–874, 872b–873b in solid tumors, 555, 556b–557b GSK3 (glycogen synthase kinase 3). See glycogen hyperlipidemia in, 871–874, 872b–873b regulation of, 601–612 synthase kinase 3 (GSK3) trans fatty acids and, 361, 362t gluconeogenesis and, 601–612 GTP (guanosine 5Ј-triphosphate) heart muscle, 947b, 948, 948f steps in, 545f, 547f in -adrenergic pathway, 441b heat glycolytic fl ux, 597f cGMP synthesis from, 459–460 production of. See thermogenesis glycolytic pathway, glycerol entry into, in olfaction, 481, 482f randomization of, 22b 597f, 671f in vision, 478–479, 479f heat of vaporization, 47, 48t

glycome, 15 GTPase, Gs as, 438 of water, 48–49, 48t glycomics, 267 GTPase activator proteins (GAPs), as biological heat shock gene promoters, 1061 glycophorin, 387, 390, 398f switches, 438, 440f, 442b heat shock proteins, in protein folding, topology of, 390, 390f GTPase activating proteins (GAPs), 441b–443b 146–147, 148f glycoproteins, 89, 89t, 263–264, 263f, 266–268, guanine, 10s, 282, 282t, 283f. See also purine heavy chains, immunoglobulin, 175–176, 176f 268f bases recombination in, 1050–1051 as glycoconjugates, 263 deamination of, 300f helicases, 1017 ligand binding of, 387 guanine nucleotides, biosynthesis of, regulatory in mismatch repair, 1030, 1030f, 1031f membrane, 267–268. See also membrane mechanisms in, 914–915, 914f in replication, 1017, 1019t, 1020 proteins guanosine, 283s Helicobacter pylori, lectins and, 271–272, 271f, oligosaccharide linkage to, 266–268, 267f, 387, in splicing, 1071, 1072f 273f 1141–1142, 1142f guanosine 3Ј,5Ј-cyclic monophosphate. See cGMP helix in protein targeting, 1141–1142 (guanosine 3Ј,5Ј-cyclic monophosphate) . See helix sugar moieties of, 387 guanosine 5Ј-diphosphate (GDP). See GDP double topology of, 390, 390f (guanosine 5Ј-diphosphate) DNA, 30, 31f, 288–290, 289f, 290f. See also glycosaminoglycans, 260–262, 261f, 262t guanosine 5Ј-diphosphate, 3Ј-diphosphate DNA structure in proteoglycans, 263–268, 264f (ppGpp), 308, 308s supercoiling and, 985–994, 987f. See also glycosidases, retaining, 222 guanosine 5Ј-monophosphate (GMP), 283s, 308, 308s DNA, supercoiling of glycoside, standard free-energy changes of, 509t guanosine nucleotide–binding proteins. in transcription, 1058f glycosidic bonds, 252 See G protein(s) underwinding of, 987, 987f phosphorolysis vs. hydrolysis reactions of, guanosine nucleotide–exchange factors (GEFs), unwinding of/rewinding of, 297–298, 297f, 613–614 426b, 442b 298f, 1012–1013, 1013f. See also DNA glycosphingolipids, 264, 366, 367f guanosine tetraphosphate (ppGpp), 308, 308s replication as glycoconjugates, 263 guanosine tetraplex, 292 variations of, 290–291, 291f N-glycosyl bonds, 282 guanosine 5Ј-triphosphate (GTP). See GTP right- vs. left-handed, 120, 121b disaccharide, 252 (guanosine 5Ј-triphosphate) RNA, 294–295, 294f, 295f hydrolysis of, 300, 300f guanylate, 282t, 283s triple, 293f glycosylated derivatives of phosphatidylinositol guanylin, 460 of collagen, 124f, 126t, 127, 128b–129b (GPI), as lipid anchor, 394, 394f, 399 guanylyl cyclases, 459–460, 459f of DNA, 292, 293f glycosylation, in protein targeting, 1141–1142, in vision, 480 helix-loop-helix, 1163–1164, 1164f 1142f guide RNA, 1111 helix-turn-helix, 1162, 1163f glyoxylate, 656–659, 657 Guillemin, Roger, 930 helper T cells, 175, 175t BMInd.indd Page I-20 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-20 Index

heme, 158 hereditary nonpolyposis colon cancer, 1038b HMG-CoA reductase, in cholesterol synthesis, 860, from aminolevulinate, biosynthesis of, 905f hereditary optic neuropathy, Leber’s, 767 869–871 defi nition of, 158 herpes simplex virus, DNA polymerase of, HMG-CoA reductase inhibitors, 872b–873b free, 158–159 1026–1027 HMG-CoA synthase, in cholesterol synthesis, 860 in oxygen binding, 158–159. See also Hers disease, 617t HMG proteins, 1178f, 1179 hemoglobin-oxygen binding Hershey, Alfred D., 288 Hoagland, Mahlon, 1104 as source of bile pigment, 904–906, 907f Hershey-Chase experiment, 288 Hodgkin, Dorothy Crowfoot, 658, 680f structure of, 158–159, 159f heterochromatin, 1175 Holden, Hazel, 180 heme a, 736s heterolytic cleavage, of covalent bonds, 512, 512f Holley, Robert W., 1104, 1118f heme b, of Complex II, 740 heteroplasmy, 767 Holliday intermediates, 1040–1041, 1042f heme c, 736s heteropolysaccharides, 254, 260–262, 262t. See in homologous genetic recombination, heme cofactors, of cytochromes, 735, 736f also polysaccharide(s) 1040–1041, 1042f heme group, 132–133, 133f heterotrophs, 4, 5f, 501 resolution of, 1048–1049, 1048f hemiacetals, 245, 247f heterotropic ligand binding, 166 in site-specifi c recombination, 1047, 1047f hemiketals, 245, 247f heterozygosity, allelic, 173 Holliger, Philipp, 1093 hemin-controlled repressor (HCR), 1185 hexadecanoic acid, 358t holoenzyme, 190 hemocytoblasts, 163 hexokinase, 220s, 548, 593t homeobox, 1163 hemoglobin catalytic activity of, 219–220, 220f homeobox-containing genes, 1190–1191 amino acids of, 8f, 9 forms of, 602–603 homeodomain, 1163, 1163f genetic variations of, 172 regulatory, 602–603 homeostasis, 589 glycated, 250b–251b hexokinase I, 602, 617 homeotic genes, 1188, 1190–1191, 1191f, 1192f as oligomer, 141 kinetic properties of, 603, 603f homing, 1089 R-state, 163–165, 165f, 171–172, 172f hexokinase II, 602, 617 homocystinuria, 717t sickle-cell, 172–174, 173f hexokinase IV, 603, 617, 940 homogentisate dioxygenase, 721 structure of, 141, 163–165, 163f, 164f, in glucose regulation, 953f, 954 homologous genetic recombination, 1038–1046. 172–173, 173f kinetic properties of, 603–604, 603f See also DNA recombinatin conformational changes in, 163–165, 165f, 166f regulation of, 603–604, 603f functions of, 1039, 1043 subunits of, 163, 163f, 164f hexose(s), 244 site-specifi c, 1038, 1046–1049, 1047f, 1048f T-state, 163–165, 165f, 171–172, 172f derivatives of, 249–251, 249f homologous proteins, 106 hemoglobin A, structure of, 173, 173f phosphorylated, in glycolysis, 546–548 homologs, 38, 106 hemoglobin–carbon dioxide binding, 170–171 structure of, 244f homolytic cleavage, of covalent bonds, 512, 512f hemoglobin–carbon monoxide binding, hexose monophosphate pathway, 575. See also homoplasmy, 767 162, 163, 167 pentose phosphate pathway homopolysaccharides, 254–259. See also glycogen; hemoglobin glycation, 250b hexose phosphates, movement of, 826, 826f polysaccharide(s); starch hemoglobin-hydrogen binding, 170–171, 170f hibernation, fatty acid oxidation in, 676b functions of, 255–257 hemoglobin-oxygen binding, 158–174. See also HIF (hypoxia-inducible transcription factor), in structure of, 254f, 256f, 257–259, 257f, 258f, protein-ligand interactions cancerous tissue, 556b 259f, 260f 2,3-bisphosphoglycerate in, 171–172, 172f high-density lipoproteins (HDLs), 865f, homotropic ligand binding, 166 Bohr effect in, 170 865t, 869 homozygosity, allelic, 173 carbon dioxide in, 170–171 defi ciency of, 874 Hoogsteen pairing/positions, 292, 293f in carbon monoxide poisoning, 168b–169b in reverse cholesterol transport, 873–874, 874f hop diffusion, 398 conformational changes in, 163–165, 165f, 166f high mobility group (HMG) proteins, 1178f, 1179 horizontal gene transfer, 106 cooperative, 163–169, 166f high-performance liquid chromatography (HPLC), hormonal cascade, 937, 938f fetal, 171 92 hormone(s), 929–971 heme in, 158–159, 159f highly repetitive DNA, 984 adrenocortical, 933t, 935 hemoglobin transport and, 163–169 Hill, Archibald, 167 autocrine, 933 models of, 167–169, 170f Hill coeffi cient, 167, 167f, 592, 592t bioassays for, 930–932 MWC (concerted), 167–168, 170f Hill equation, 167 in carbohydrate metabolism regulation, sequential, 168–169, 170f Hill plot, 167, 167f 624–626, 626f myoglobin in, 159, 159f Hill reaction, 770 lipid metabolic integration with, 626 pH in, 170–171, 170f, 171 Hill reagent, 770 catecholamine, 933t, 934–935. See also quantitative description of, 159–162, 160f, 167 hippurate, 709, 710s catecholamines structural factors in, 163–165, 163f, 164f HIRA, in chromatin remodeling, 1176t in cholesterol regulation, 869–871, 870f T-state to R-state transition in, 163–165, 165f, his operon, 1169 classifi cation of, 933–936, 933t 171–172, 172f histamine, 909 defi nition of, 929 hemoglobin S, 172–174 histidine, 10s, 79s, 81, 721–722, 898 discovery of, 930, 931b hemoglobin transport in amino acid biosynthesis, 898–899, 903f diversity of, 933–936, 933t of hydrogen, 169–171 as buffer, 65, 65f eicosanoid. See eicosanoids of oxygen, 163–169. See also hemoglobin-oxygen conversion of, to -ketoglutarate, endocrine, 933, 933t binding 721–722, 721f endocrine glands and, 936–937, 936f hemophilia, 234, 235f properties of, 77t, 81 excitatory effects of, 446 hemoproteins, 89t titration curve for, 85, 85f in fat metabolism regulation, 626 Henderson-Hasselbalch equation, 64–65, 84 histone(s), 994, 994–1000, 995f, 995t functions of, 929–930 Henri, Victor, 201 acetylation/deacetylation of, 1175–1176 in gene regulation, 453–454, 456f, Henseleit, Kurt, 704 chromatin and, 994, 996f, 998b–999b, 1182–1184, 1183f heparan sulfate, 261, 264–266, 265f 1175–1176. See also chromatin in carbohydrate and fat metabolism, 624–626 heparin, 234, 261–262, 261s, 262f in chromosomal scaffold, 999 in glycogen phosphorylase regulation, 621–622, hepatic enzymes, 939–943 in gene regulation, 1175–1176 622f hepatocyte, 939 in nucleosomes, 996f, 997f, 1000f, 1175–1176. inhibitory effects of, 446 amino acid metabolism in, 941–942 See also nucleosomes lectin binding of, 269 carbohydrate metabolism in, 624–626, 626f positioning of, 996–997 mode of action of, 932–933, 932f, 933t epinephrine cascade in, 443–444, 444f properties of, 995, 995t as neurotransmitters, 930 fatty acid metabolism in, 941–942, 943f types of, 995, 995t nitric oxide as, 933t, 936 fatty acid synthesis in, 843 variant, 995, 998b–999b oligosaccharide moieties of, 269 glucose metabolism in, 940–941, 941f histone acetyltransferases (HATs), 1176 overview of, 929–930 glycogen granules in, 613, 613f histone deacetylases (HDACs), in chromatin paracrine, 933, 933, 933t glycogen in, 256 remodeling, 1176 eicosanoid, 371–372, 371f NADPH synthesis in, 839, 840f histone tails, 996, 996f peptide, 934 nutrient metabolism in, 939–943 Hitchings, George, 923, 923f synthesis of, 934 triacylglycerol recycling in, 850, 850f HIV/AIDS, 218–219, 1088, 1089b regulation of, 936–937 heptahelical receptors, 438. See also GPCRs HMG-CoA, 687 release of, 936–937, 938f heptoses, 244 in cholesterol synthesis, 860 feedback inhibition of, 937 BMInd.indd Page I-21 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-21

response time for, 933 of 1,3-bisphosphoglycerate, 520, 520s cells of, 174–175, 175t retinoid, 933t, 936 of disaccharides, 252–253 cellular, 174 sex, 372, 372s, 475s, 933t, 935 free energy of, 517–519, 520f, 521–522, 521f, clonal selection in, 175 steroid, 372, 372s 521t, 522f evolution of, 1049–1051 synthesis of, 874, 874f of glucose 6-phosphate, by glucose 6-phospha- humoral, 174 in signaling, 453–454, 930, 930f, 932f, 933. See tase, 614–615, 615f integrins in, 471 also signaling; signaling proteins of glycosidic bonds, vs. phosphorolysis reaction, oligosaccharides in, 270–271, 270f hormonal cascade in, 937, 938f 613–614 in plants vs. animals, 476, 476f signal amplifi cation in, 933, 937, 938f of oxygen esters, 522f selectins in, 270, 270f steroid, 372, 372f, 372s, 933t, 935 of phosphocreatine, 520, 521f immunization, viral vaccines in, 1088 receptor for, 1173f, 1183–1184 of phosphoenolpyruvate, 520, 520f immunoblot assay, 178f, 179 synthesis of, 874, 874f, 875f of phosphorylated compounds, 520–521, 521t immunodefi ciencies synthesis of, 874, 874f, 875f of polysaccharides and disaccharides, to mono- drugs for, 1089b mitochondrial, 763–764 saccharides, 558–560, 569f immunofl uorescence, 333–334, 334f target organs of, 936f of thioesters, 521, 521f immunoglobulin(s) (Ig), 174. See also response time of, 933 hydronium ions, 58, 81 antibodies thyroid, 933t, 936 hydropathy index, 392–393 heavy chains of, 176, 176f, 177 in transcription regulation, 471–472, 472f hydropathy plot, 392f recombination in, 1050–1051 transport of, in blood, 949–950 hydrophilic compounds, 50, 50t light chains of, 176, 176f, 177 in triacylglycerol synthesis, 669–670, 670f, 671f, hydrophobic compounds, 9, 50, 50t recombination in, 1049–1051, 1051f, 1052f 849–850, 850f solubility in water, 50–53, 52f, 53f structure of, 176, 176f, 1050–1051 tropic, 937 hydrophobic interactions, 53, 54t, 116. See also immunoglobulin A, 176 water-insoluble, 932–933 weak interactions immunoglobulin D, 176, 177 hormone receptor, 932–933 in amphipathic compounds, 52–53, 52f immunoglobulin E, 176, 177 hormone-receptor binding, 932–933, 932f. See also in globular proteins, 132, 132f immunoglobulin fold, 176, 177 receptor-ligand binding in protein stability, 116–117 immunoglobulin G, 175–177, 176f, 177f Scatchard analysis of, 435b, 932 -hydroxy--methylglutaryl-CoA. See HMG-CoA immunoglobulin genes, recombination of, hormone response elements (HREs), 471, -hydroxyacyl-ACP dehydratase, 837f, 838 1049–1051, 1051f 1182, 1183t -hydroxyacyl-CoA (3-hydroxyacyl CoA), 674 immunoglobulin M, 176, 176f, 177 host range, 1174t -hydroxyacyl-CoA dehydrase, 674 immunoprecipitation, 335, 335f Housay, Bernardo, 616b -hydroxyacyl-CoA dehydrogenase, 674 IMP. See inosinate (IMP) housekeeping genes, 1156 -hydroxybutyrate, 686 importins, 1144 HOX genes, 1190–1191, 1195 in brain metabolism, 949 in vitro evolution (SELEX), 1093, 1095b, 1117b HOXA7, 1191 hydroxylases, 844b in vitro studies, limitations of, 9 HPLC (high-performance liquid 5-hydroxylysine, 81, 82s inborn errors of metabolism, 369b chromatography), 92 in collagen, 128b–129b indirect immunofl uorescence, 333–334, 334f HREs (hormone response elements), 1182, 1183t 5-hydroxymethylcytidine, 284s indirubicin, 491b Hsp70 family, in protein folding, 146–147, hydroxyproline, 81, 82s, 128b–129b, 129s induced fi t, 157 147f, 148f in collagen, 127, 128b–129b in antigen-antibody binding, 177–178, 177f HU, in replication, 1019, 1019t, 1020f hyperammonemia, 709 in enzyme-substrate binding, 198, human immunodefi ciency virus infection, 218–219, hypercholesterolemia, 868, 871–873, 872b–873b 219–220, 220f 1088, 1089b hyperchromic effect, 297–298 inducers, 1160 humoral immune system, 174. See also immune hyperglycemia, insulin secretion in, 951–953, 952f inducible gene products, 1156 system hyperinsulinism-hyperammonemia syndrome, 702 induction, 1156 hunchback, 1189f hyperlipidemia, 871–873, 872b–873b industrial-scale fermentation, 566–568 Huntington disease, protein misfolding in, 150 in heart disease, 871–874, 872b–873b infl uenza hyaluronan, 260–261 trans fatty acids and, 361, 362t drug therapy for, 271, 271f hyaluronate, 261s, 262t, 266f hypertonic solutions, 56–57, 56f lectins and, 270–271 hyaluronic acid, 260–261, 261s, 262t, 266f hypochromic effect, 297–298 selectins and, 270–271 hyaluronidase, 261 hypoglycemia, 950, 951f information theory, 23 hybrid duplexes, 299 hypothalamic-pituitary axis, 936–937, 938f informational macromolecules, 15 hybridization. See cloning; DNA hybridization hypothalamus, 936–937, 936f, 937f inhibition feedback Hycamptin (topotecan), 992s, 993b in body mass regulation, 961–962, 961f concerted, 900 hydrazine, in anammox reaction, 884b–885b hypotonic solutions, 56–57, 56f cumulative, 889 hydride ion, 530 hypoxanthine, from adenine deamination, 300f sequential, 900 hydrocarbons, 12 hypoxanthine-guanine phosphoribosyltransferase, inhibitory G protein, 446 hydrogen 922 inhibitory proteins, in ATP hydrolysis during hemoglobin transport of, 169–171 hypoxia, 171, 546, 760–761 ischemia, 760, 760f

hydrogen bonds, 9, 48. See also bond(s) adaptive responses in, 760–761 initial velocity (rate) (V0), 200–201, 201f directionality of, 50, 50f reactive oxygen species and, 760–761 initiation codons, 1107, 1107f. See also codons examples of, 50t hypoxia-inducible transcription factor (HIF), in protein synthesis, 1127–1129, 1129f formation of, 49–50, 116–117 761, 761f initiation complex, 1128 in ice, 48–49, 49f in cancerous tissue, 556 in bacteria, 1127–1128, 1128f low-barrier, 218 in eukaryotes, 1128–1129, 1130f, 1131t of nucleic acid base pairs initiation factors, 1131t, 1184 in DNA, 286–287, 287f, 288, 289f, 290f I initiator sequences, 1177–1178 in RNA, 296f I bands, 181, 181f Inman, Ross, 1012

number of, 116 ibuprofen, 846, 846s inorganic phosphate (Pi). See phosphate, with polar hydroxyl groups, 49–50 ice, hydrogen bonds in, 48–49, 49f inorganic in polysaccharides, 256f, 258–259, 258f icosatetraenoic acid, 358t inorganic pyrophosphatase, in plants vs. properties of, 47–50, 49f idose, 246s animals, 819–820

in water, 47–50, 48f–50f, 55f iduranate, 261, 261s inorganic pyrophosphate (PPi), 819–820 as weak interactions, 54–55, 54t, 55f IgA, 176 inosinate (IMP), 912 hydrogen ion(s) IgD, 176, 177 in anticodons, 1109–1110, 1110f concentration of, 59–61, 60f, 60t. See also pH IgE, 176, 177 biosynthesis of AMP and GMP from, 914f from water ionization, 58–63 IgG, 175–177, 176f purine ring of, 912f hydrogen sulfi de IgG genes, recombination of, 1050–1051, 1051f inosine, 284s, 1112 solubility in water, 51, 51t IgM, 176, 176f, 177 inositol hydrolases, 65 Illumina sequencer, 341–342, 342f in lipid synthesis, 855, 855f

hydrolysis, 65, 69, 69f imatinib mesylate, 491b inositol 1,4,5-trisphosphate (IP3), 370–371, of acetyl-CoA, 521, 521f, 521t immune system, 174–179 447–448, 450f ATP. See ATP hydrolysis antigen-antibody interactions in, 174–179 Inr (initiator) sequences, 1177–1178 BMInd.indd Page I-22 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-22 Index

insect viruses, recombinant gene expression in, patch-clamp studies of, 421 isozymes, 549, 602, 602b 323, 324f voltage-gated, 421, 422–424 ISWI family, in chromatin remodeling, 1176t insects, recombinant gene expression in, 323 in signaling, 424, 436f, 437, 464–469, insertion mutations, 1027 464f, 466f insertion sequences, 1049 vs. transporters, 404, 404f J insertion site, 1014 ion concentration, in cytosol vs. extracellular J segment, of kappa light chain, 1050–1051, 1051f Insig, 870 fl uid, 465t Jacob, François, 293, 1159, 1159f insulin, 934 ion-exchange chromatography, 90, 91f, 93t Jagendorf, André, 787 amino acid sequence of, 97–99 ion gradients, 414–418, 416f, 417f JAK-STAT pathway, 457–458, 457f

in cholesterol regulation, 869–871, 870f ion product of water (Kw), 59, 60 leptin in, 962–963 in diabetes mellitus, 959 ion pumps/transporters. See ATPase(s); membrane Janus kinase (JAK), 457–458, 457f, 962, 963f discovery of, 931b transport; transporter(s) Januvia (sitagliptin), 970t in gene regulation, 453–457, 456f, 608–609, ionic interactions, 9, 54, 54t. See also weak jasmonate, 372–373, 475, 475s, 847 609t, 1184 interactions jellyfi sh, fl uorescent proteins in, 448b–449b in carbohydrate and fat metabolism, 624–626 protein stability and, 116–117 Jencks, William P., 197 in glucose regulation, 453–457, 951–953, 952t, in solutions, 50–51 Jetten, Mike, 884b 953f ionization Joyce, Gerald, 1093 in glucose transport, 408b equilibrium constants for, 59 jumping genes, 1039, 1049 glycogen synthase kinase 3 mediation of, 624, 624f peptide, 86–87, 86f junk DNA, 1096b in glycogen synthesis, 456, 456f of water, 58–63 leptin and, 963–964, 964f equilibrium constant for, 59 in lipid metabolism, 869–871, 870f ionization constant. See dissociation constant (Ka) K as peptide hormone, 934 ionizing radiation, DNA damage from, 300 Kϩ. See potassium in signaling, 453–457, 934, 934f ionophores, 418 k (Boltzmann constant), 507t synthesis of, 934, 934f ionotropic, 468 k (rate constant), 194

in triacylglycerol synthesis, 849–850, 849f IP3 (inositol 1,4,5-trisphosphate), 370–371, activation energy and, 194 in weight regulation, 963–964, 965f 447–448, 450f, 452f Ka (association constant), 160 insulin insensitivity, 959, 964–965, 968–971 IPTG (isopropylthiogalactoside), 1160, 1160s in Scatchard analysis, 435b insulin pathway, 453–457, 456f irinotecan (Campto), 992s, 993b Kaiser, Dale, 317 insulin receptor, 453–457, 456f iron, heme, 158–159, 159f. See also heme light chains, 176, 176f, 1050–1051, 1051f

insulin receptor substrate-1 (IRS-1), 454, 456, 456f iron protoporphyrin IX, 736s kcat, 205, 205t integral membrane proteins, 389–394. See also iron regulatory proteins, 642b kcat/Km (specifi city constant), 205, 205t membrane proteins iron response elements (IREs), 642b–643b Kd (dissociation constant), 160–162 integrins, 266, 266f, 402, 470–471, 470f iron-sulfur centers, 641, 735–736, 736f in Scatchard analysis, 435b intermediate, 217 in aconitase, 641, 642f Kendrew, John, 131, 134b–135b, 141, 141f intermediate fi laments, 8, 8f reaction, 777–778 Kennedy, Eugene P., 638, 732, 853, 853f internal guide sequences, 1082, 1083f iron-sulfur proteins, 735 Kennedy cycle, 853

intervening sequences, 343, 984, 984f. Rieske, 735, 741f Keq. See equilibrium constant (Keq) See also intron(s) IRP1, 642b keratan sulfate, 261, 261s intestinal glucose transporter (GLUT2), IRP2, 642b -keratin 406–407, 407t, 417f, 418, 953–954 irreversible inhibitor, 210 in hair, 126, 126f intrinsic factor, 681 IRS-1 (insulin receptor substrate-1), 454, 456, 456f structure of, 126–127, 126f intrinsic pathway, 233 ischemia, ATP hydrolysis during, inhibitory ketals, 245–246, 247f intrinsically disordered proteins, 141–142, 142f, 760 proteins in, 760, 760f -keto acid, decarboxylation of, 513s introns, 343–344, 343f, 984, 984f, 1070 islet cells, pancreatic, 953–955, 953f -keto acid dehydrogenase complex, branched- enzymatic properties of, 1082–1083, 1084f islets of Langerhans, 931b, 953f chain, 723 evolutionary signifi cance of, 1088–1089 isocitrate, 641s ketoacidosis, diabetic, 558, 688, 711, 960 homing by, 1089, 1090f formation of, via cis-aconitate, 641, 641f ketoaciduria, branched-chain, 717t

as mobile elements, 1089, 1090f oxidation of, to -ketoglutarate and CO2, -ketoacyl-ACP reductase, 837f, 838, 839f self-splicing, 1070–1072, 1093 641–644, 643f -ketoacyl-ACP synthase, 837f, 838, 839f enzymatic properties of, 1082–1085, 1084f isocitrate dehydrogenase, 534t, 641–644, -ketoacyl-CoA, 674 evolutionary signifi cance of, 1093 643f, 643s -ketoacyl-CoA transferase, 306, 687 spliceosomal, 1072, 1074f reaction mechanism of, 643f ketogenic amino acid, 711 splicing of, 1069–1075, 1070f, 1072f–1074f isocitrate lyase, 657 -ketoglutarate, 129b, 129s, 641 transcription of, 1070 isoelectric focusing, 94, 95f in amino acid biosynthesis, 891f, 892, 894f inverted repeat DNA, 291–292, 292f isoelectric pH (point) (pI), 77t, 84, 95t glucogenic amino acids in, 574t ion(s) determination of, 94, 95f oxidation of isocitrate to, 641–644, 643f

blood levels of, 950 isolated system, 21 oxidation to succinyl-CoA and CO2, 644 hydride, 530 isoleucine, 79, 79s, 717, 722, 898 transfer of -amino groups to, 699, 699f as intracellular messengers, 468 biosynthesis of, 897f, 898–899 -ketoglutarate dehydrogenase, 534t, 568t ion channels, 403f, 404–405, 420–426, 421 catabolic pathways for, 674, 675f, 718f, 722f, 723f -ketoglutarate dehydrogenase complex, 644 Ca2ϩ, 420–421, 424 conversion of, to succinyl-CoA, 722, 722f ketohexoses, 245, 246f ClϪ properties of, 77t, 79 / forms of, 246, 247f in cystic fi brosis, 415b, 424 isomer(s) ketone(s), 12, 529s in signaling, 468 confi gurational, 16–18, 16f, 17f hemiacetals and, 245, 247f current measurement in, 421 geometric, 16–17 hemiketals and, 245, 247f defective, 424–426 L, 245 ketone bodies, 686–688, 942 in cystic fi brosis, 415b isomerases, 560 conversion of amino acids to, 711, 711f Kϩ, 422–424, 422f, 466f phosphoglucose, 593t in diabetes mellitus, 688, 711 defective, diseases caused by, 426t phosphohexose, reaction of, 549f in fasting/starvation state, 688, 949f, 958 in signaling, 465–466, 466f, 468 triose phosphate, 593t in liver, 686–688, 688f ligand-gated, 421, 424 isomerization, 513–514, 514f in muscle contraction, 945, 945f, 948, 948f in insulin secretion, 955f isopentenyl pyrophosphate, 874–875, 875f ketoses, 244, 244f in membrane transport, 424 in cholesterol synthesis, 860–861, 861f, 862f D isomers of, 245, 246f in signaling, 424, 436f, 437, 464f, 466f, 469f isoprene, in cholesterol synthesis, 859, 860–862, L isomers of, 245 membrane potential and, 464–465, 464f 860f, 862f nomenclature of, 245 Naϩ, 424 isoprenoids ketosis, 688, 711, 959–960 defective, diseases caused by, 426t as lipid anchors, 394, 394f Khorana, H. Gobind, 304, 1106, 1106f in signaling, 465–467, 466f, 468 synthesis of, 874–875, 875f kidney neurotransmitter, 468 isopropylthiogalactoside (IPTG), 1160, 1160s aquaporins of, 418–420, 419t nicotinic acetylcholine receptor as, 424 isoproterenol, 438s as endocrine organ, 936f operation of, 464–465 isotonic solutions, 56–57, 56f glutamine metabolism in, 702–703 BMInd.indd Page I-23 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-23

Kilby, B. A., 215 leukemia, 895–897 digestion, mobilization, and transportation of, killer T cells, 175, 175t leukocytes, 174, 175t, 949–950, 950f 668–672, 668f, 670f, 671f kinase(s), 516, 548, 593t, 646b. See also protein leukotrienes, 371f, 372, 847, 933t, 935. See also ether, 364, 365f kinases and specifi c type, e.g., hexokinase eicosanoids synthesis of, 856–857, 858f kinesins, 179 Levinthal, Cyrus, 145 extraction of, 377–378, 377f kinetoplast, 983 Levinthal’s paradox, 145 functions of, 833 Klenow fragment, 1017 lexA repressor, in SOS response, 1169–1170 hepatic metabolism of, 941–942

Km (Michaelis constant), 202, 203f, 204t, 205t LHC (light-harvesting complex), 773, 773f hydrolysis of, 378 apparent, 209t Li-Fraumeni cancer syndrome, 492 intestinal absorption of, 668–669 calculation of, 203, 206 life, origin of, 33–35, 33f, 34f, 1092–1094, 1117b. membrane, 268, 268f, 362–370, 363f. See also interpretation of, 203–205 See also evolution membrane lipids Köhler, Georges, 178, 178f ligand(s), 157. See also protein-ligand as oxidation-reduction cofactors, 374–375 Kornberg, Arthur, 616b, 1013, 1013f interactions as pigments, 370, 376, 376f Koshland, Daniel, 168, 198 binding site for, 157–158, 1165 separation of, 377f, 378 Krebs, Hans, 633, 704 concentration of, 161–162 in signaling, 370 Krebs bicycle, 707, 707f ligand-gated ion channels, 421, 424. See also ion solubility of, 51, 52–53, 52f, 387, 388f Krebs cycle, 633. See also citric acid cycle channels storage, 357–362, 363f. See also fatty acid(s);

Kt (Ktransport), 406 in membrane transport, 424 waxes Kuenen, Gijs, 884b in signaling, 424, 436f, 437, 464f, 466f, 469f transport of, 857–858, 864–871, 867f Kunitz, Moses, 190 ligand-gated receptor channels, 424 lipid anchors, 264, 387, 394, 394f Kupffer cells, 939 defective, 426t lipid rafts and, 399

Kw (ion product of water), 59, 60 open/closed conformation of, 468, 469f lipid bilayer, 387–389, 387f, 388f in signaling, 466f, 467–468, 469f formation of, 387, 388f synaptic aggregation of, 398 liquid-ordered/disordered state of, 395–396, 395f L ligand-receptor binding. See receptor-ligand lipid catabolism, in cellular respiration, 634f L isomers, 245 binding lipid metabolism, 588f L-19 IVS ribozyme, 1082–1083, 1084f ligase, 646b in adipose tissue, 849–850, 850–852, 851f, 936f, lac operon, 1159–1160, 1159f, 1160f, 1162, 1162f light 943–944 regulation of, 1165–1167, 1166f absorption of, 771–776, 773f in brain, 949 lac promoter, 1162, 1162f chemical changes due to, 300, 301f cortisol in, 958–959 Lac repressor, 1162, 1166 chlorophylls in, 771–773, 772f, 773f in endoplasmic reticulum, 840f, 842, 843 DNA-binding motif of, 1162, 1163f, 1164f by DNA, 297–298 epinephrine in, 958, 959t -lactam antibiotics, resistance to, 224, 225f by photopigments, 772f, 773–774, 773f. gene expression in, insulin and, 624–626 -lactamases, 224, 225f See also photopigments in liver, 941–942, 943f lactate, 516s, 563. See also lactic acid fermentation by proteins, 80b, 80f in muscle, 945, 945f, 948f in muscle contraction, 946, 948 reaction centers in, 774–775, 775f regulation of lactate dehydrogenase (LDH), 516s, 533f, 534t, visible allosteric and hormonal, 626 563, 602b as electromagnetic radiation, 771 xylulose 5-phosphate in, 606 lactic acid fermentation, 546 electromagnetic radiation of, 771f lipid rafts, 399, 399f in muscle contraction, 946 light absorption lipid toxicity hypothesis, 969–970, 969f pyruvate in, 563–565 chlorophyll in, 774–775, 775f lipidomes, 15, 379 Lactobacillus bulgaricus, in fermentation, 566 light chains, immunoglobulin, 176, 176f lipidomics, 379–380, 380t lactonase, 576 recombination in, 1050–1051, 1051f, 1052f lipoate (lipoic acid), 635, 635s, 635f lactose, 253, 253f light-dependent reactions (of photosynthesis), 769 in pyruvate dehydrogenase, 635–637 lactose intolerance, 561 light-driven electron fl ow, 776–786. See also lipopolysaccharides, 268, 268f. See also lactose transporter (lactose permease), electron fl ow, light-driven polysaccharide(s) 416, 416f, 416t light energy, harvesting of. See photosynthesis lipoprotein(s) lactosylceramide, 367f light-harvesting complex (LHC), 773, 773f classifi cation of, 865t ladderanes, 885 light-harvesting molecules, 774 functions of, 865 lagging strand, 1013, 1013f light reactions, 769 high-density, 865f, 865t, 869 lambda light chains, immunoglobulin, 176f lignin, 908 low-density, 865f, 865t, 866–867 lambda phage vector, 315t lignoceric acid, 358t properties of, 865t Lambert-Beer law, 80b Lind, James, 128b, 128f prosthetic groups of, 89, 89t lamellae, 770 Lineweaver-Burk equation, 204 transport of, 864–871, 867f lanolin, 362 linkage analysis, 347–349 very-low-density, 865f, 865t, 866–867 lanosterol, 862 linkers, 317–318, 317f lipoprotein lipase, 265f, 669 large fragment, of DNA polymerase I, 1017 linking number (Lk), 988–989, 988f, 996 liquid-ordered/disordered state, 395–396, 395f lauric acid, 358t linoleate, 843f, 845 lithotropes, 884b Lavoisier, Antoine, 505 synthesis of, 842f liver LDH. See lactate dehydrogenase (LDH) linoleic acid, 358t alanine transport of ammonia to, 702–703, 703f LDL (low-density lipoprotein), 865f, 865t, 867 oxidation of, 677, 678f branched-chain amino acids in, 723, 723f LDL receptor, 867, 868, 868f linolenate, 843f, 845 cholesterol synthesis in, 864 leading strand, 1012, 1013f lipase, 360 detoxifi cation in, 943 Leber’s hereditary optic neuropathy (LHON), 767 lipid(s), 15, 357–380. See also fatty acid(s) epinephrine cascade in, 443–444, 444f lecithin. See phosphatidylcholine analytical techniques for, 377–380, 377f, 379f glutamate release of ammonia in, 700–702, 702f lecithin-cholesterol acyl transferase (LCAT), 869 annular, 391, 392f glyceroneogenesis in, 849f, 850–852, 851f lectins, 269–273, 270f–273f attachment to membrane proteins, 264, 387, glycogen in, 256 Leder, Philip, 1106 394, 394f breakdown of, 614–615, 614f, 616b, 617t leghemoglobin, 888 biosynthesis of, 833–876 ketone bodies in, 686–688, 688f Lehninger, Albert, 638, 732, 732f acetyl-CoA in, 833, 834f, 835f, 838–839, metabolism in, 939–943, 940f Leloir, Louis, 615, 616b 951–953 of amino acids, 941–942, 941f leptin, 960, 961–964, 961f–964f eicosanoid synthesis in, 845–847, 846f of carbohydrates, 624–626, 626f insulin and, 963–964, 964f fatty acid synthesis in, 833–845. See also of fatty acids, 941–942, 943f leptin receptor, 961 fatty acid synthesis of glucose, 940–941, 941f, 952f, 955–956, 956t Lesch-Nyhan syndrome, 922 glyceroneogenesis in, 850–852, 851f of glutamine, 702–703 Letsinger, Robert, 304 insulin in, 951–953 muscle and, 945, 948f leu operon, 1169 membrane lipid synthesis in, 852–859 triacylglycerol recycling in, 850, 850f leucine, 79, 79s, 717, 898 subcellular localization of, 840f liver enzymes, 939–943 biosynthesis of, 897f, 898–899 triacylglycerol synthesis in, 848–850 liver X receptor (LXR), 871 catabolic pathways for, 674, 675f, 718f, 723f classifi cation of, 379–380, 380t living organisms. See bioorganisms properties of, 77t, 79 components of, 8f Lk (linking number), 988–989, 988f, 996 leucine zipper, 1163, 1164f dietary, intestinal absorption of, 668f Lobban, Peter, 317 BMInd.indd Page I-24 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-24 Index

Lon, 1107 maltoporin, structure of, 393f fl uidity of, 395–396, 395f London forces, 53 maltose, 252, 253, 253f functions of, 385 loops (hairpins) formation of, 252, 252f lipid bilayer of, 387–389, 387f in DNA, 292, 292f, 999, 1000f structure of, 252, 252s overview of, 385 in replication fork, 1012, 1012f mammalian cell cultures, 323 permeability of, 387 in RNA, 295, 295f, 1065f, 1084–1085 mammals plasma, 3, 3f lovastatin (Mevacor), 872b–873b fat stores in, 361 bacterial, 5, 6f low-barrier hydrogen bond, 218 signaling in, 474t composition of, 386–387, 386f, 386t low-density lipoprotein (LDL), 865f, mannosamine, 249–250, 249s lipid rafts in, 398–399, 399f 865t, 867 mannose, 245, 246s lipopolysaccharides of, 268, 268f low-density lipoprotein receptor, 867 epimers of, 246s microdomains of, 398–399, 399f luciferin, activation of, 525b oxidation of, 249f, 250 neuronal, transport across, 949 lutein, 773, 774s structure of, 246s permeability of, 56 luteinizing hormone, 269 mannose 6-phosphate, 272–273, 272f protein targeting to, 1142, 1143f lyase, 646b MAP kinase kinase (MAPKK), 455, 456f syndecans in, 264, 264f lymphocytes, 174, 175t, 950, 950f MAP kinase kinase kinase (MAPKKK), 455, 456f polarization of, 464–465, 464f B, 175, 175t, 950 MAPK cascade, 455, 456 structure of, 387–389 recombination in, 1049–1051, 1052f in JAK-STAT pathway, 457f, 458 trilaminar appearance of, 387 functions of, 175 in plants, 475–476, 475f, 476f types of, 386f helper, 175, 175t MAPKs, 455, 456f membrane-bound carriers, mitochondrial electron receptors for, 175 maple syrup urine disease, 717t, 723 passage through, 735–737, 736f, 737f selectins and, 270, 270f mapping. See also genome sequencing sequence of, 736–737, 737f T, 175, 175t, 950 denaturation, 1012 standard reduction potential of, 737, 737t antigen binding by, 175 genetic, of E. coli, 1010f membrane dynamics, 395–402 cytotoxic, 175, 175t mass-action ratio (Q), 509, 593, 760 membrane fusion, 400–401, 400f, 401f Lynen, Feodor, 862, 863f in carbohydrate metabolism, 593t membrane glycoproteins, 267 lysine, 79s, 81, 717, 898 in oxidative phosphorylation, 760 membrane lipids, 268, 268f, 362–370, 363f, 386, biosynthesis of, 896f, 898–899 mass spectrometry, 100–102 386t. See also lipid(s) carbamoylation of, in rubisco, 802–804, 804f in amino acid sequencing, 100–102, 101f, 102f abnormal accumulation of, 369b catabolic pathways for, 718f in carbohydrate analysis, 274, 275f aggregations of, 387, 388f properties of, 77t, 81 electrospray, 101, 101f amphipathicity of, 362, 398f structure of, 79s in lipid analysis, 378–379, 379f of archaea, 365–366, 366f lysolecithin, 869s matrix-assisted laser desorption/ionization, 101 in bilayer, 387–388, 387f, 388f lysophospholipases, 368, 368f tandem, 101, 102f classifi cation of, 363f lysosomes, 6, 7f mass-to-charge ratio (m/z), 100 diffusion of, 396–398, 396f–398f protein targeting to, 1142, 1143f maternal genes, 1188–1190, 1189f catalysis of, 396–397, 396f lysozymes, 260 maternal mRNA, 1188–1190 fl ip-fl op, 396–397, 396f catalytic activity of, 220–222, 222f, 223f mating-type switch, 1174t lateral, 397–398, 397f reaction mechanism of, 223f matrix-assisted laser desorption/ionization mass distribution of, 387, 389f, 403f structure of, 133t spectrometry (MALDI MS), 101, 274, 275f ether lipids, 364, 365f lyxose, 246s Matthaei, Heinrich, 1105 glycolipids, 268, 268f, 363, 363f mature onset diabetes of the young (MODY2), glycosphingolipids, 264 611b–612b, 768 head groups of, 363, 852–853, 854f, M Maxam, Alan, 302 855–856, 857 M line (disk), 181, 181f Maxam-Gilbert sequencing, 302 in liquid-ordered/disordered state,

M-protein, 182 maximum velocity (Vmax), 201–205, 201f 395–396, 395f Mackinnon, Roderick, 422, 422f MB isozyme, 947b lysosomal degradation of, 368, 368f MacLeod, J. J. R., 931b McArdle disease, 617t membrane protein attachment to, 387 macrocytes, 714 McCarty, Maclyn, 288 microdomains of, 398–399, 399f macromolecules McClintock, Barbara, 344, 1038, 1038f orientation of, 387, 387f informational, 15 McElroy, William, 525b phospholipids, 363, 363f energy requirements of, 524–525 McLeod, Colin, 288 in plants, 365, 365f weak interactions in, 54–55, 55f MCM proteins, 1025 plasmalogens, 364, 365f macrophages, 174, 175t, 177, 177f MDR1 (multidrug transporter), 413 in rat hepatocyte, 386f in insulin resistance, 969f mechanism-based inactivators, 210 in signaling, 371–372, 371f in plaque formation, 872f Mediator, 1179 sphingolipids, 366–368, 367f mad cow disease, 150b–151b medicine. See also specifi c disorders sterols, 363f, 368–370, 368f magnesium complex, ATP and, 518, 518f genomics in. See genome sequencing, medical synthesis of, 852–859 magnesium ions, in Calvin cycle, 802–803, 803f, applications of cytidine nucleotides in, 853, 853f, 854f 804, 805, 810–811, 811f personalized genomic, 39, 340b, 350–351 in Escherichia coli, 853–855, 854f major facilitator superfamily (MFS), 416 megaloblastic anemia, 714 in eukaryotes, 855–856, 855f–857f major groove, 289, 289f megaloblasts, 714 head group attachment in, 852–853, 853f, 854f malaria, sickle-cell anemia and, 174 meiosis, 1041–1046, 1042, 1043f–1044f, 1046f head-group exchange reaction in, 855–856, malate, 647 in bacteria, 1039–1041 857f oxidation of, to oxaloacetate, 647 crossing over in, 1043, 1043f, 1045b salvage pathways in, 856 transport of, 840 in eukaryotes, 1041–1043, 1043f in vertebrates, 855–856, 856f, 857f malate-aspartate shuttle, 708, 758–759, 758f fetal, errors in, 1045b in yeast, 855, 856f malate dehydrogenase, 534t, 570, 647 recombination in, 1039–1046, 1043f transport of, 857–858. See also membrane

in C4 pathway, 816–818 MEK, 455, 456f transport malate synthase, 657 melanocortin, 962 membrane lipopolysaccharides, 268, 268f MALDI MS (matrix-assisted laser desorption/ -melanocyte-stimulating hormone membrane permeability, 56 ionization mass spectrometry), 101, (-MSH), 962 membrane polarization, in signaling, 445f, 464–467, 274, 275f Mello, Craig, 1185, 1185f 464f, 466f

maleic acid, 16–17, 16s melting point membrane potential (Vm), 403, 403f, 464–465, 464f malic enzyme of common solvents, 48t in signaling, 464–469, 464f, 468

in C4 pathway, 815f, 816 of water, 47, 48–49, 48t membrane proteins, 3, 386f, 386t, 387 in NADPH synthesis, 839, 840, 840f membrane(s), 3, 3f aggregation of, 398, 398f malonyl/acetyl-CoA–ACP transferase, asymmetry of, 387, 387f, 388 helix of, 391, 392 837f, 838 common properties of, 387 amphitropic, 390 malonyl-CoA, 679, 679f, 833s, 842 composition of, 386–387, 386f, 386t attachment of, 390–391, 391f as inhibitor of carnitine acyltransferase I, 679, 679f fl exibility of, 395 lipid anchors in, 264, 387, 394, 394f, 398–399 synthesis of, 834f, 838 fl uid mosaic model of, 387, 387f prenylation in, 861f, 875 BMInd.indd Page I-25 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-25

barrels in, 137f, 391, 393–394 messenger RNA. See mRNA (messenger RNA) methionine, 79, 79s, 722, 898 sheets in, 392 metabolic acidosis, 61, 67–68, 68b, 688 biosynthesis of, 896f, 898–899 carbohydrate linkage to, 266–268, 266f, 387 metabolic alkalosis, 61, 68b conversion of, to succinyl-CoA, 722, 722f functional specialization of, 386f, 387 metabolic control, 592 properties of, 77t, 79 hydropathy index for, 392–393 metabolic control analysis, 596–602, 597 synthesis of, 714f hydrophilic interactions of, 387–388, 388f of carbohydrate metabolism, 598–600, methionine adenosyl transferase, 712 hydrophobic interactions of, 387–388, 388f, 598b–599b synthesis of, 714f 390–392 increased fl ux prediction by, 598b–599b methotrexate, 923, 924s integral, 389–394, 391f, 392f quantitative aspects in, 598b–599b 1-methyladenine, demethylation of, 1033, 1035f attachment of, 390–391, 391f metabolic fuels, body stores of, 956t methyladenosine, 284s in cell-cell interactions/adhesion, 402 metabolic pathways, 28, 502, 588f, 942t. See also methylamine, pKa of, 83, 84f functions of, 402 specifi c pathways, e.g., pentose phosphate methylation proteoglycans as, 263–268, 264f pathway of amino acid residues, 1136, 1137f structure of, 391–394, 391f anabolic in DNA mismatch repair, 1029–1030, lipid attachment to, 264, 387, 394, 394f in glycogen metabolism, 613–614 1029f–1031f in lipid bilayer, 387, 387f vs. catabolic pathway, 503f enzyme, 229 membrane-spanning, 390–394, 390f–393f catabolic of nucleotide bases, 302 orientation of, 387, 387f, 391 in glycogen metabolism, 613–614 5-methylcytidine, 284s, 302 peripheral, 389 vs. anabolic pathway, 503f methylcytosine structure of, 390–394, 391f–394f de novo, 910–922 deamination of, 299–300, 300f topology of, 390, 391–394, 391f–394f endogenous, 867 demethylation of, 1033, 1035f amino acid sequence and, 390f, 391 exogenous, 866 methylguanosine, 284s transbilayer diffusion of, 398, 398f glycolytic. See glycolysis 6-N-methyllysine, 81, 82s transport, 393, 402–427. See also transporter(s) regulation of, 502, 587–627 methylmalonic acidemia (MMA), 717t, 724b–725b Trp residues in, 393, 393f adenine nucleotides in, 594–596 methylmalonyl-CoA, 678 Tyr residues in, 393, 393f enzyme activity in, 589–592, 590f methylmalonyl-CoA epimerase, 678 weak interactions of, 390–391, 391f, 392f mechanisms of, 588f methylmalonyl-CoA mutase, 678 membrane rafts, 399, 399f near-equilibrium and nonequilibrium steps in, Mevacor (lovastatin), 872b–873b in signaling, 463 592–593, 592f, 593t mevalonate, in cholesterol synthesis, 860–861, membrane-spanning proteins, 390–394, 390f–393f steady state maintenance in, 589 860–861, 860f, 861f, 869 membrane transport, 402–427 salvage, 856, 857f, 910–911, 922–923 Meyerhof, Otto, 544 activation energy for, 403–404, 404f metabolic regulation, 592 Mg2ϩ. See also magnesium active, 409–418 metabolic syndrome, 969–971 in biochemical standard state, 507 ATP energy in, 525–526 metabolic water, 69 in Calvin cycle, 802–803, 803f primary, 403f, 409, 409f metabolism, 28, 502 complex with ATP, 518, 5118f secondary, 403f, 409, 409f in adipose tissue, 936f, 943–944 as enzyme cofactor, 407, 407f aquaporins in, 418–420, 419t, 420f aerobic, of vertebrates, 564b MGDG (monogalactosyldiacylglycerol), 365f ATP-driven, 409–414, 411f–413f amino acid, 588f micelles, 52–53, 52f, 387, 388f ATP synthases in, 412 anaerobic, of coelacanths, 564b Michaelis, Leonor, 201, 201f, 202 2ϩ Ca pump in, 410–411, 411f ATP in, 28, 28f Michaelis constant (Km), 202–206, 203f, 204t, 205t chloride-bicarbonate exchanger in, 398, 398f, bioenergetics and, 506–511 apparent, 209t 407–409, 407f blood in, 949–950 interpretation of, 203–204, 203–205 cotransport systems in, 409, 409f in brain, 948–949, 949f Michaelis-Menten equation, 203, 203f in diabetes, 408b carbohydrate. See carbohydrate metabolism Michaelis-Menten kinetics, 203–207, 591 direction of, 403f carbon-carbon bond reactions in, 512–513, microRNA (miRNA), 1081, 1185 electrochemical gradient in, 403, 403f 512f, 520f microarrays electrogenic, 409 cellular, transformations in, 511–512 DNA, 337–338, 337f, 338f electroneutral, 409 energy, 588f oligosaccharide, 274, 275f by facilitated diffusion, 403f. See also feedback inhibition in, 29 microbes, gut, obesity and, 968 transporter(s) folate, as chemotherapy target, 924f microdomains, 398–399 free-energy change in, 409–410 free radical reactions in, 514–515 microtubules, 8, 8f, 179 of glucose glutathione, 908f Miescher, Friedrich, 288 in erythrocytes, 405–407, 405f, 406f glycogen. See glycogen, metabolism of mifepristone, 471, 472s transporters for, 405–407, 405f, 406f, group transfer reactions in, 515–516, 515f Miller-Urey experiment, 33–34, 33f 407t, 408f hepatic, 939–943, 940f Milstein, Cesar, 178, 178f ion channels in, 403f, 420–426. See also ion intermediary, 502 mineralocorticoids, 935 channels internal rearrangements in, 513–514, 514f synthesis of, 874, 874f, 875f ion gradients in, 414–418, 416f, 417f lipid. See lipid metabolism minichromosome maintenance (MCM) ionophore-mediated, 403f, 418 in muscle, 944–948, 945f, 948f proteins, 1025 kinetics of nitrogen. See nitrogen metabolism Minkowski, Oskar, 931b in active transport, 409–410 nucleotide, 588f minor groove, 289, 289f in passive transport, 404, 404f, 405–407, 406f overview of, 501–504 miRNA (microRNA), 1081, 1185 lectins in, 272–273 oxidation-reduction reactions in, 516, 516f mirror repeat DNA, 292, 292f of lipids, 857–858 regulation of, 28–29, 592 mismatch repair, 1028–1030, 1028t, 1029f–1031f membrane potential in, 403, 403f metabolite(s), 3, 14–15, 502 missense mutations, 1111 modes of, 403f, 404f, 425t secondary, 15 Mitchell, Peter, 731, 747, 748f NaϩKϩ ATPase in, 411–412, 412f metabolite concentration, regulatory enzyme mitochondria, 6, 7f, 983 neuronal, 949 response to, 592f, 593, 593t aging and, 732, 766 passive, 402–409, 404 metabolite fl ux, change in enzyme activity on, in apoptosis, 764–765, 764f porins in, 393, 393 597, 597f ATP synthase complex in, 750 rate of, 403, 405–406, 406f metabolite pools, in plants, 826, 826f ATP synthesis in, 732. See also ATP synthesis SERCA pump in, 410–411 metabolome, 15, 591, 591f oxidation in, 683f by simple diffusion, 403, 403f metabolomics, 15 biochemical anatomy of, 732–734, 733f in targeting, 1141–1142. See also protein metabolon, 656 chemiosmotic theory applied to, 748f targeting metal cluster, 785 classes of cytochromes in, 735, 736f transporters in, 404–409. See also transporter(s) metal ion catalysis, 200, 220, 221f DNA in, 765f

menaquinone (vitamin K2), 374, 375s metalloproteins, 89, 89t electron-transfer reactions in, oxidative Menten, Maud, 201, 201f, 202 metamerism, 1188 phosphorylation and, 732–747. See also Merrifi eld, R. Bruce, 102–103, 103f, 304 metformin (Glucophage), 970t electron-transfer reactions, mitochondrial Meselson, Matthew, 1011 methane, 529s evolution of, 36, 37f Meselson-Stahl experiment, 1011, 1011f methanol, in lipid extraction, 377f, 378 from endosymbiotic bacteria, 765–766, 765f

mesophyll cells, in C4 plants, 815f, 817 methanol poisoning, 208 functions of, 732, 762–765 BMInd.indd Page I-26 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-26 Index

mitochondria (Continued) enantiomers of, 244, 245f metabolism in, 944–948, 945f, 948f genetic code variations in, 1108b–1109b epimers, 245, 246f red, 944–945 heteroplasmy and, 767 families of, 244, 244f in regulation of carbohydrate metabolism, homoplasmy and, 767 in glycolysis, 561–563, 571f 626, 626f hypoxic injury of, 761 Haworth perspective formulas for, 247–248, slow-twitch, 944 lipid metabolism in, 839, 840, 840f 247f–249f structure of, 181–183, 181f, 182f matrix of, 733, 733f hemiacetal, 245, 247f white, 944–945 membranes of, 732, 733f hemiketal, 245, 247f muscle contraction, 182–183, 183f mutations in, 765f, 766–768 heptose, 244 ATP in, 525–526 apoptosis and, 764–765 hexose, 244 creatine phosphate in, 946b diseases associated with, 732, 767–768 hydrolysis of polysaccharides and disaccharides fuel for, 945–948, 945f, 948f endosymbiotic bacteria and, 765–766, 765f to, 558–560, 569f muscle fi bers, structure of, 181–183, 181f nitrous acid and, 301, 301f intermediates of, 249f, 250–251 muscle proteins, 179–184, 180f–183f oxidative stress and, 745–746, 745f ketose, 244, 244f mutagenesis plant, alternative mechanism for NADH L isomers of, 245 oligonucelotide-directed, 324, 325f oxidation in, 746, 746b–747b nomenclature of, 244, 245, 250 site-directed, 323–324 protein targeting to, 1142–1143 oxidation of, 249f, 250, 251 mutarotation, 248 reactive oxygen species and, pentose, 244 mutases, 560 745–746, 745f phosphorylation of, 251 mutations, 32, 299, 979, 1027. See also genetic in respirasomes, 743 pyranoses, 246–247, 248f, 249f defects respiratory proteins and, 766t reducing, 251, 252–253 alkylating agents and, 301f, 302 shuttle system transport of cytosolic NADH into, stereoisomers of, 244–245, 245f apoptosis and, 764–765 758–759, 758f, 759f structure of, 245–251, 246f–249f cancer-causing, 489–494, 493f, 656, 1027–1028, in thermogenesis, 762–763 tetrose, 244 1037b–1038b transport of fatty acids into, 670–672, 671f triose, 244, 244f citric acid cycle, in cancer, 656 uncoupled, heat generated by, 762–763, 763f moonlighting enzymes, 642b deletion, 1027 in xenobiotics, 763–764 morphogens, 1188 endosymbiotic bacteria and, 765–766, 765f mitochondrial DNA (mtDNA), 765–768 motifs, 137–140, 139f–140f. See also protein folding in error-prone translesion DNA synthesis, evolution of, 765 motor proteins, 179–184, 180f–183f 1034–1037 genetic code variations in, 1108b–1109b mRNA (messenger RNA), 281, 1057. in evolution, 32–33, 32f, 37–38, 1194b–1195b mutations in, 765f, 766–768, 767f, 768f. See also RNA in fatty acyl–CoA dehydrogenase, 682 See also mitochondria, mutations in artifi cial, in genetic code studies, 1105 insertion, 1027 structure of, 765, 765f base pairing of, with tRNA, 1109–1110, 1110f mechanism of, 1035f mitochondrial encephalomyopathy, 767–768 degradation of, 1084–1085, 1136 missense, 1111 mitochondrial inheritance, 766–767 differential processing of, 1075–1077 mitochondrial, 301, 301f, 732, 764–768, 765f. mitochondrial respiration, 812 early studies of, 293–294 See also mitochondria, mutations in mitosis, 484, 484f editing of, 1111–1113 nonsense, 1134b mixed-function oxidases, 685, 720, 843, 5Ј cap of, 1070 oncogenic, 489–494, 493f, 656, 1027–1028, 844b–845b functions of, 293–294 1037b–1038b mixed-function oxygenases, 844b hairpin loops in, 1065f, 1084–1085 oxidative stress and, 745–746, 745f mixed inhibitor, 208, 208f, 209f, 209t length of, 294 radiation-induced, 300, 301f MjtRNATyr, 1126b maternal, 1188, 1188–1190 resistance of genetic code to, 1110–1111 MjTyrRS, 1126b monocistronic, 294, 294f silent, 1027, 1111 MMA (methylmalonic acidemia), 717t polycistronic, 294, 294f substitution, 1027 mobile elements, 1039–1040, 1049 polypeptide coding by, 293–294 suppressor, 1134b introns as, 1089, 1090f poly(A) tail of, 1075, 1075f transition, 1111 modularity, 434 processing of, 1069–1077. See also RNA wild-type, 33 modulators, in protein-ligand binding, 166 processing in translation. MutH, in DNA mismatch repair, 1029–1030, 1030f, MODY (mature onset diabetes of the young), stability of, 589–590 1031f, 1038b 611b–612b, 768 synthesis of, rate of, 589 MutL, in DNA mismatch repair, 1029–1030, 1030f, molecular biology, central dogma of, -MSH (-melanocyte-stimulating hormone), 962 1031f, 1038b 977, 977f, 1086 mtDNA (mitochondrial DNA), 765–768, 983, MutS, in DNA mismatch repair, 1029–1030, 1030f, molecular chaperones, 146–147, 146f, 147f, 1108b–1109b. See also mitochondrial DNA 1031f, 1038b 1143, 1145f (mtDNA) MWC model, of protein-ligand binding, molecular evolution, 104–108. See also evolution mTORC1, 965, 966f 167–168, 170f amino acid sequences and, 104–108, 106f–108f mucins, 267 myelin sheath, components of, 386, 386t amino acid substitutions in, 106 Mullis, Kary, 327 myocardial infarction, 948 homologs in, 106–107 multidrug transporter (MDR1), 413 myoclonic epilepsy with ragged-red fi ber disease horizontal gene transfer in, 104 multienzyme complex(es) (MERRF), 768 molecular function, of proteins, 332 in oxidative phosphorylation myocytes, 944 molecular logic of life, 2 Complex I (NADH: ubiquinone oxidoreductase), glucose in, control of glycogen synthesis from, molecular mass, 14b 738, 738t, 739f 598–600 molecular parasites, evolution of, 1094 Complex II (succinate dehydrogenase), myofi brils, 181, 181f molecular weight, 14b 740, 740f myoglobin, 131–133, 132f, 159, 159f molecules. See biomolecules Complex III (ubiquinone: cytochrome c heme group in, 132–133, 133s monocistronic mRNA, 294 oxidoreductase), 740–742, 741f in oxygen binding, 159, 162, 162f. See also monoclonal antibodies, 178 Complex IV (cytochrome oxidase), hemoglobin-oxygen binding Monod, Jacques, 167, 293, 1159, 1159f 742–743, 742f structure of, 131–133, 132f, 159, 159f, 163, 163f monogalactosyldiacylglycerol (MGDG), 365f electron carriers in, 737–743 nuclear magnetic resonance studies of, monooxygenases, 844b substrate channeling through, 655–656, 655f 135b–136b, 135f, 136f monophosphates, nucleoside, conversion of, to multifunctional protein (MFP), 684 x-ray diffraction studies of, 134b–135b, nucleoside triphosphates, 916 multimer, 140 134f–135f monosaccharides, 243, 243–251. See also multipotent stem cells, 1192 subunits of, 163, 163f carbohydrate(s) multisubunit proteins, 87, 87t myosin, 179–181, 180f. See also actin-myosin abbreviations for, 252t muramic acid, 249f entries aldose, 244, 244f muscle coiled coils in, 126 anomers, 246 alanine transport of ammonia from, 703, 703f in muscle contraction, 182–183, 183f in aqueous solutions, 245 creatine/creatinine in, 946b–947b phosphorylation of, 487–488 chiral centers of, 244–245, 245f, 246f energy sources for, 945–948, 945f, 948f structure of, 179–181, 180f, 181f conformations of, 248, 249f fast-twitch, 944 in thick fi laments, 180f, 181, 182–183, 183f D isomers of, 245, 246f gluconeogenesis in, 943–944, 948, 948f myosin-actin interactions, 182–183, 183f derivatives of, 249–251, 249f heart, 947b, 948, 948f myristic acid, 358t BMInd.indd Page I-27 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-27

myristoyl groups, membrane attachment of, neuronal signaling, 930, 930f NO. See nitric oxide (NO) 394, 394f neuropathy, optic, Leber’s hereditary, 767 nocturnal inhibitor, 804 m/z (mass-to-charge ratio), 100 neuropeptide Y (NPY), 962 nodules, nitrogen-fi xing, 887–888, 887f neurotransmitters Noller, Harry, 1103, 1103f biosynthesis of, from amino acids, 908–909, 910f nomenclature systems N as hormones, 930 D, L, 18 N (Avogadro’s number), 507t receptors for, 468 RS, 18 N-linked oligosaccharides, 267, 267f, release of, 468 Nomura, Masayasu, 1115, 1115f 1141–1142, 1142f membrane fusion in, 401, 401f noncoding DNA, 342–344, 984. See also introns

N2. See nitrogen neutral fats. See triacylglycerol(s) noncoding RNA (ncRNA), 1186 Naϩ. See sodium ion(s) neutral glycolipids, 363f, 366, 367f noncompetitive inhibition, 208, 208f, 209f, 209t Naϩ-glucose symporter, 417, 417 neutral pH, 59 noncovalent bonds, 9. See also weak interactions NADϩ (nicotinamide adenine dinucleotide), 307s newborn, PKU screening in, 721 nonequilibrium steps, in metabolic pathway, in Calvin cycle, 809 Nexavar, 491b 592f, 593 reduced form of. See NADH next-generation sequencing, 304, 339–342, nonessential amino acids, 892. See also ultraviolet absorption spectrum of, 533f 341f, 342f amino acid(s)

NADH, 602b NH3. See ammonia nonoxidative reaction, of pentose phosphate cytosolic, shuttle systems acting on, 758–759, niacin (nicotinic acid), 535, 535s pathway, 577–580, 578f 758f, 759f dietary defi ciency of, 535 nonpolar compounds. See hydrophobic dehydrogenase reactions and, 532–535, 533f niche, 1192 compounds oxidation of, in plant mitochondria, 746, nick translation, 1017, 1017f, 1018, 1023, 1024f, nonreducing sugars, 252, 253 746b–747b 1028t, 1031–1032, 1033f nonsense codons, 1107, 1107f. See also codons in payoff phase of glycolysis, 550–555, 553f, 554f nicotinamide, 535s nonsense mutations, 1134b ultraviolet absorption spectrum of, 533f nicotinamide adenine dinucleotide (NADϩ), 307s nonsense suppressors, 1134b NADH dehydrogenase, 674, 738, 738t, 739f. See reduced form of. See NADH nonsteroidal anti-infl ammatory drugs (NSAIDs), also Complex I nicotinamide adenine dinucleotide phosphate. 371–372, 845–847, 846s NADH:ubiquinone oxidoreductase, 738, 738t, 739f. See NADPϩ norepinephrine, 909, 934 See also Complex I nicotinamide nucleotide–linked dehydrogenases, 734 as neurotransmitter vs. hormone, 930 NADPϩ, 533s reactions catalyzed by, 734t Northrop, John, 190 dehydrogenase reactions and, 532–533, 533f, nicotine, 535s novobiocin, 992b 534t nicotinic acetylcholine receptor, 424, 467–468 NPY (neuropeptide Y), 962 reduced form of. See NADPH defective, 426t NS domains, 264f, 265, 265f vitamin form of, defi ciency of, 535 open/closed conformation of, 468, 469f NSAIDs (nonsteroidal anti-infl ammatory drugs), NADPH, 28f, 602b in signaling, 467–468, 469f 371–372, 845–847, 846s in anabolic reactions, 839 synaptic aggregation of, 398 NuA4, in chromatin remodeling, 1176t in Calvin cycle, 801f, 804 nicotinic acid (niacin), 535, 535s nuclear localization sequence (NLS), in cell protection against oxygen derivatives, dietary defi ciency of, 535 1144, 1144f 576b, 576f Niemann-Pick disease, 369b, 869 nuclear magnetic resonance (NMR) spectroscopy dehydrogenase reactions and, 532–533, 533f Niemann-Pick type-C, 869 in carbohydrate analysis, 274, 275f in fatty acid synthesis, 838–839 Nirenberg, Marshall, 1105–1106, 1105f in protein structure determination, 135b–136b, in glucose oxidation, 575–577, 576b, 577f nitrate reductase, 882, 883f 135f, 136f in glyceraldehyde 3-phosphate synthesis, 801f, nitric oxide (NO), 460 nuclear proteins, targeting of, 1143–1145, 1144f 804–805 as hormone, 933t, 936 nuclear receptors, 436f, 437 in partitioning of glucose 6-phosphate, 580, 580f solubility in water, 51 nucleases, 1013 in photosynthesis, 808–812, 808f–811f, 839 synthesis of, arginine as precursor in, 909, 911f nucleic acid(s), 15. See also DNA; RNA synthesis of nitric oxide (NO) synthase, 460, 936 bases of. See base(s), nucleotide/nucleic acid; in adipocytes, 839, 840f nitrifi cation, 882 base pairs/pairing in chloroplasts, 839 nitrifying bacteria, 884b–885b chemical synthesis of, 305, 305f in cytosol, 839, 840f nitrite reductase, 882, 883f components of, 8f in hepatocytes, 839, 840f nitrogen evolution of, 33–34, 1092–1094 NaϩKϩ ATPase, 411–412, 412f, 417, 417f available, nitrogen cycle maintenance of, 882, 5Ј end of, 285, 285f in membrane polarization, 464, 464f 882f hydrophilic backbones of, 285, 285f, 288 in retina, 477 cycling of, 502, 502f long, 286 in membrane transport, in neurons, 949 enzymatic fi xation of nomenclature of, 282, 282t, 284 nalidixic acid, 992b, 992s nitrogenase complex in, 882–888, 886f, 887f nonenzymatic transformation of, 299–302 nanos, 1188–1189 excretion of, 704–710, 705f, 706f, 707f, 709f, 710f nucleotides of, 281–287. See also nucleotide(s) naproxen, 846, 846s reduction of, to ammonia, 882–883 phosphate bridges in, 284–286, 285f National Center for Biotechnology Information solubility in water, 51, 51t phosphodiester linkages in, 284–286, 285f (NCBI), 342 nitrogen cycle, 882 polarity of, 285, 285f native conformation (protein), 31, 116 available nitrogen in, 882 pyrimidine bases of, 282–284, 284f natural selection, 33 bacteria in, 884b short, 286 ncRNA, 1186 nitrogen fi xation, 822–888, 882f, 883f, 886f, 887f structure of, 287–297 Neanderthals, genome sequencing for, 350b–351b nitrogen-fi xing nodules, 887–888, 887f base properties and, 286–287, 296 near-equilibrium steps, in metabolic pathway, nitrogen metabolism, 881–891 in DNA, 287–293. See also DNA structure 592–593, 592f ammonia in, 888–889 overview of, 287–297 nebulin, 182 available nitrogen in, 882, 882f in RNA, 294–295, 294f–296f Neher, Erwin, 421, 421f biosynthetic reactions in, 910f schematic representation of, 285–286 Nernst equation, 530–531 enzymatic fi xation in, 882–888, 886f, 887f synthesis of. See DNA replication; translation Neu5Ac, 269–270 glutamate and glutamine in, 696 3Ј end of, 285 neural transmission, steps in, 466f glutamine amidotransferases in, 890–891, 890f nucleic acid sequences neuroendocrine system, 930 glutamine synthetase in, 888–890, 889f amino acid sequence and, 980, 980f neuroglobin, 163 nitrogen mustard, as mutagen, 301f in evolutionary studies, 107 neuron(s) nitrogenase complex, 883–888 nuclein, 288 anorexigenic, 962 enzymes of, 886f nucleoids, 3, 3f, 5, 6f, 1002 gustatory, 481, 483f, 484f nitrogen fi xation by, 882–888, 882f, 883f, 886f, nucleophiles, in enzymatic reactions, ion channels in, 465–467, 467f 887f 216f, 512, 512f membrane transport in, 949 nitroglycerin, 460 nucleophilic displacement reaction, of ATP, Naϩ channels in, 424, 466f nitrous acid, as mutagen, 301, 301f 523–524, 524f olfactory, 481, 482f nitrovasodilators, 460 nucleoside(s), 281 orexigenic, 962 NLS (nuclear localization sequence), 1144 nomenclature of, 282t, 284 photosensory, 477, 477f–480f NMR spectroscopy. See nuclear magnetic nucleoside diphosphate kinase(s), 526, 645, 916 visual, 477, 477f–480f resonance spectroscopy Ping-Pong mechanism of, 526, 526f BMInd.indd Page I-28 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-28 Index

nucleoside diphosphates, 306, 306f Ogston, Alexander, 648b osteogenesis imperfecta, 130 nucleoside monophosphate kinases, 916 Okazaki fragments, 1012–1013, 1013f, 1021–1022 outer membrane phospholipase A, structure of, nucleoside monophosphates, 306, 306f synthesis of, 1021–1022, 1021f 393f conversion of, to nucleoside triphosphates, 916 oleate, 677, 842–843, 843f outgroups, 346 nucleoside triphosphates, 306, 306f synthesis of, 842–843, 842f ovary, 936f hydrolysis of, 306, 307f oleic acid, 358t overweight, 960. See also body mass; obesity nucleoside monophosphate conversion to, 916 olfaction, signaling in, 481, 482f, 483f oxaloacetate, 608, 640, 840, 841f in RNA synthesis, 524 oligo (1S6) to (1S4) glucantransferase, 614. in amino acid biosynthesis, 895–898, 896f, 897f nucleosomes, 994, 995–1000, 996f, 997f, 1000f See also debranching enzyme asparagine and aspartate degradation to, acetylation of, 1175–1176 oligomers, 15, 87t, 88, 140 724, 724f

positioning of, 996–997 oligonucleotide, 286 in C4 pathway, 815f, 816 in 30 nm fi ber, 998, 1000f oligonucleotide-directed mutagenesis, 324, 325f glucogenic amino acids and, 574t 5Ј-nucleotidase, 920 oligopeptides, 86 in glyceroneogenesis, 849f nucleotide(s), 281 oligosaccharide(s), 243. See also carbohydrate(s); in glyoxylate cycle, in plants, 826, 826f abbreviations for, 282t, 283f, 306f disaccharides oxidation of malate to, 647 absorption spectra of, 286, 286f analysis of, 274, 275f oxidases, 844b in ATP hydrolysis, 306 chemical synthesis of, 274 mixed-function, 685, 720, 843, 844b–845b bases of, 281–287, 282s–284s. See also base(s), conformations of, 258–259, 259f oxidation nucleotide/nucleic acid diversity of, 269 of acetate, 650, 650f components of, 281–284, 282f–284f glycoprotein linkage to, 266–268, 267f, 387, , 685–686 depurination of, 300, 300f 1141–1143, 1142f in endoplasmic reticulum, 685f evolution of, 33–34, 1092–1094 as informational molecules, 15, 269–273, 272f in peroxisomes, 685f fl avin, 535–537, 536f, 536t, 734 lectin binding of, 269–263, 270f–273f of amino acids, 696–704. See also amino acid functions of, 306–308 N-linked, 267, 267f, 1141–1142, 1142f oxidation N-glycosyl bonds of, hydrolysis of, 300 nomenclature of, 252–253 ATP yield from, 760t linkage of, 284–286, 285f O-linked, 266–267, 267f, 1141–1142 . See oxidation metabolism of, 588f, 942t in peptidoglycan synthesis, 824f of carbon, 529f nomenclature of, 282, 282t, 283f, 284 separation and quantifi cation of, 274, 275f in citric acid cycle, energy of, 647–649, 649f, 649t nonenzymatic reactions of, 299–302, 300f, 301f structure of, 274, 275f of fatty acids, 672–686. See also fatty acid nonenzymatic transformation of, 299–302 synthesis of, 1141–1143, 1142f oxidation phosphate groups of, 281, 281f, 282t, 283f, 306 oligosaccharide microarrays, 274, 275f of glucose, 26, 575–581. See also glucose purine. See purine nucleotides omega () oxidation, 684–685, 685f oxidation pyrimidine, biosynthesis of, 915–916, 915f, 916f omega-3 fatty acids, 359 of glyceraldehyde 3-phosphate to regulation of, 916, 916f omega-6 fatty acids, 359 1,3-bisphosphoglycerate, 551–552, 553f

regulatory, 308, 308f OmpLA, structure of, 393f of isocitrate to -ketoglutarate and CO2, as second messengers, 308, 308f OmpX, structure of, 393f 641–644, 643f

sequences of, schematic representation of, oncogenes, 489, 494f of -ketoglutarate to succinyl-CoA and CO2, 644 285–286, 286f oncogenic mutations, 489–494, 493f, 656, 1027, of malate to oxaloacetate, 647 structure of, 281–284, 282f–284f, 282s, 1037b–1038b , in endoplasmic reticulum, 684–685, 685f

282t, 283s in citric acid cycle, 656 of pyruvate to acetyl-CoA and CO2, 634, 634f sugar, 615–619 one gene–one enzyme hypothesis, 642b, 980 of succinate to fumarate, 646–647 formation of, 615–616, 618f one gene–one polypeptide hypothesis, 980 oxidation-reduction reactions, 22, 516, 516f in glycogen synthesis, 615–619, 617–619, open reading frame (ORF), 1107 bioenergetics and, 528–537 618f, 620f open system, 21 dehydrogenation in, 529–530, 529f synthesis of, 890–891, 910–925, 910f operators, 1157 electromotive force and biological work in, 528 enzymes in, chemotherapeutic agents operons, 1159–1160 enzymes in, 844b–845b targeting, 923–925, 923f, 924f his, 1169 half-reactions in, 528–529 transphosphorylations between, 526–527, 526f lac, 1159–1160, 1159f, 1160f reduction potentials in, 530–531, 530f, 531t variant forms of, 284, 284s, 290–293, 291f leu, 1169 standard reduction potentials in, 531–532, 531t nucleotide-binding fold, 308 phe, 1169 oxidative deamination, 700 nucleotide-excision repair, 1028t, 1031–1032, regulation of, 1165–1167, 1166f oxidative decarboxylation, 634 1032f, 1033f, 1037b–1038b trp, 1167, 1167f oxidative pentose phosphate pathway, 575–577, in bacteria, 1028t, 1031–1032, 1033f opsins, 477. See also rhodopsin 577f, 579, 801, 811–812, 826 in humans, 1033f absorption spectra of, 480, 480f oxidative phosphorylation, 731–769. See also nucleotide sequences optic neuropathy, Leber’s hereditary, 767 phosphorylation amino acid sequence and, 980, 980f optical activity, 18b, 77 ATP hydrolysis inhibition in, 760, 760f in evolutionary studies, 107 ORC (origin replication complex), 1025 ATP-producing pathways in, 761–762, 762f schematic representation of, 285–286, 286f ordered water, 53, 53f ATP synthesis in, 747–749. See also ATP nucleotide sugar, 819 orexigenic neurons, 962 synthesis nucleotide triplets. See codons ORF (open reading frame), 1107 ATP yield in, 760t nucleus, 3, 3f organelles, 6–8, 6f brown adipose tissue heat production in, protein targeting to, 1143–1145, 1144f cytoskeleton and, 8–9, 8f 762–763, 763f NURF, in chromatin remodeling, 1175 in plants, 800–801, 801f cellular energy needs in, 760 Nüsslein-Volhard, Christiane, 1187, 1187f organic solvents, in lipid extraction, 377–378, 377f chemical uncouplers of, 749, 749f nutrients, transport of, in blood, 949–950 Orgel, Leslie, 1092, 1092f chemiosmotic theory of, 731 oriC (DNA replication origin), 1020–1021, 1020f in heart muscle, 948 in bacteria, 1012, 1012f mitochondria in, 731–747 O in eukaryotes, 1025 electron-transfer reactions of, 732–747. O-glycosidic bond, 252 origin-independent restart of replication, 1041 See also electron-transfer reactions, O-linked oligosaccharides, 266–267, 267f, origin of replication (ori), 318 mitochondrial 1141–1142 origin replication complex (ORC), 1025 gene mutations of, 766–768

O2. See oxygen ornithine, 81, 82s apoptosis and, 764–765 O6-methylguanine ornithine -aminotransferase, 892, 894f endosymbiotic bacteria and, 765–766, 766f mutation from, 1033, 1035f ornithine decarboxylase, 211b–212b, 909 oxidative stress and, 745–746, 745f O6-methylguanine-DNA methyltransferase, 1033, ornithine transcarbamoylase, 706 photophosphorylation and, 732. See also 1035f orotate, 911 photophosphorylation obesity, 960–971. See also body mass orthologs, 38, 106, 333 reactive oxygen species and, 745–746, 745f gut bacteria and, 968 oseltamivir, 271 regulation of, 759–762 SCD1 in, 843 osmolarity, 56–57, 56f oxidative photosynthetic carbon cycle, 815 Ochoa, Severo, 616b, 1085, 1085f osmosis, 56–57, 56f oxidative stress octadecadienoic acid, 358t osmotic lysis, 56–57 mitochondria in, 745–746, 745f octadecanoic acid, 358t osmotic pressure, 56f, 57 oxidoreductase, 534 BMInd.indd Page I-29 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-29

oxygen pentose phosphate pathway, 575, 745, 801, pH optimum, 67 cycling of, 501–502, 502f 811–812, 825–826 pH scale, 60 electron transfer to, 529–530 general scheme of, 577f phagocytosis, 177, 177f hemoglobin binding of, 158–174. See also glucose 6-phosphate in, 577–580, 578f, 579f, 580f pharmaceuticals. See under drug and hemoglobin-oxygen binding glycolysis and, 580, 580f specifi c drugs partial pressure of, 162 NADPH in, 575–580, 577f phase variation, 1173, 1173f solubility in water, 51, 51t in NADPH synthesis, 839, 840f phe operon, 1169 oxygen-binding proteins, 158–174 nonoxidative reactions of, 577–580, 578f phenotype, 979 oxygen consumption, ATP synthesis and, overview of, 575 phenotypic functions, of protein, 331–332 chemiosmotic coupling in, 755–757 oxidative, 575–577, 577f, 579, 801, 811–812, 826 phenylacetate, 709, 710s oxygen ester, free-energy hydrolysis of, 521, 522f reductive, 579, 801 phenylacetyl-CoA, 709, 710s oxygen-evolving complex, 784–785, 785f in Wernicke-Korsakoff syndrome, 580 phenylacetylglutamine, 709, 710s water split by, 784–785 pentose phosphates phenylalanine, 79, 79s, 717, 898 oxygen transport, in blood, 163, 949–950 movement of, 826, 826f biosynthesis of, 898, 902f oxygenases, 844b synthesis of, in Calvin cycle, 805–806, 806f–808f, catabolic pathways for, 718f, 719f, 720f mixed-function, 844b 808–809 alternative, 719–721, 720f oxytocin, 938f PEP. See phosphoenolpyruvate (PEP) degradation of, to acetyl-CoA, 717–719, 718f pepsinogen, 697 genetic defects in, 718–721, 720f peptic ulcers, 271f, 272 in phenylketonuria, 719–721 P peptide(s), 75, 85–88. See also polypeptide(s); properties of, 77t, 79 P-450 enzymes, 763–764, 844b, 845b, 943 protein(s) phenylalanine hydroxylase, 719, 898 mitochondria and, 763 amino acid residues in, 81, 82s, 87 role of tetrahydrobiopterin in, 719, 720f in xenobiotics, 763–764 ionization behavior of, 86–87 phenylketonuria (PKU), 717t, 719 P (peptidyl) binding site, ribosomal, 1128 naming of, 86f newborn screening for, 721 P cluster, 883 size of, 87 phenylalanine in, alternative catabolic pathways P glycoprotein, 413, 414f standard free-energy changes of, 509t for, 719–721, 720f P/2eϪ, ratio, 755 structure of, 86f, 87–88 phenylpyruvate, 720 P/O ratio, 755 synthesis of, 102–104, 103f, 104t pheophytin, 776 P-type ATPases, 410–411, 411f, 463 titration curves of, 87 pheophytin-quinone reaction center, 776–777, 777f P-type Ca2ϩ pump, 410–411, 411f peptide bonds, 86f, 117–119, 120f. See also angle, secondary structures and, 123–124, 124f p27 protein, 142 bond(s) Phillips, David, 221 p53 mutations, 492 in helix, 120f, 122 Phillips mechanism, 221–222 p53 protein, 142, 142f cis confi guration of, 123, 124f phosphagens, 527 Pace, Sidney, 1083 electric dipole in, 118f, 122 phosphatase, 646b Paganini, Niccolò, 130 formation of, in protein synthesis, phosphate pair-rule genes, 1188, 1190 1129–1130, 1132f as buffer, 61f, 62–63, 63f, 65–66 Palade, George, 1140, 1140f properties of, 117–119 inorganic palindromic DNA, 291–292, 292f trans confi guration of, 124f in cells, 518t palmitate peptide group, 118, 118f in glucose oxidation, 26 desaturation of, 842–843, 842f peptide hormones, 933t, 934, 934f in photosynthesis, 809–810, 809f in fatty acid synthesis, 842, 842f peptide prolyl cis-trans isomerase (PPI), as possible energy source, 518t, 527 synthesis of, 834, 836f, 838–839, 838f in protein folding, 147 in starch synthesis, 820–821, 821f palmitic acid, 358t peptide translocation complex, 1140, 1141f in nucleotides, 281, 281f palmitoleate, synthesis of, 842–843, 842f peptidoglycans, 262t, 823–824 variant forms of, 284, 284f palmitoleic acid, 358t bacterial synthesis of, 823–824, 824f triose, interconversion of, 550, 552f palmitoyl-CoA, 842 penicillin and, 224 phosphate bond, high-energy, 522 oxidation of, ATP in, 674–675, 676t structure of, 823, 823f phosphate translocase, 757 palmitoyl groups, membrane attachment of, 394, 394f peptidyl (P) binding site, ribosomal, 1128 phosphatidate, in triacylglycerol synthesis, pancreas, 936f peptidyl transferase, 1132 849, 849f in glucose regulation, 953–955 perilipin, 669, 670f, 961f phosphatidic acid, 363, 364f, 388f, 849 pancreatic cells, 953, 953f peripheral membrane proteins, 389–390 synthesis of, 848f, 849, 853 pancreatic cells, 953–955, 953f permanent waves, 127b in triacylglycerol synthesis, 849, 849f pancreatic enzymes, 697–698, 698f, 699 permeability transition pore complex (PTPC), 764 phosphatidic acid phosphatase, in triacylglycerol pancreatic trypsin inhibitor, 699 permeases, 404. See also transporter(s) synthesis, 849, 849f pancreatitis, acute, 232, 699 pernicious anemia, 681, 713 phosphatidylcholine, 363, 364f, 367f, 367s, 843, paracrine hormones, 933 peroxisome(s), 6, 7f, 682 843f, 855, 869s eicosanoid, 371–372, 371f oxidation in, 685–686 membrane distribution of, 388 paralogs, 38, 106, 333 oxidation in, 682–683, 683f phosphatidylethanolamine, 363, 364f paralysis, toxic, 424–426 in plants, 683, 683f in lipid synthesis, 854f, 855, 856, 856f Paramecium, membrane components in, 386t lipid metabolism in, 840f membrane distribution of, 388, 389f paramyosin, 182 peroxisome proliferator-activated receptors synthesis of, 848–849, 848f parasites, molecular, evolution of, 1094 (PPARs), 679–682, 842, 965–966, phosphatidylglycerol, 363, 364f parathyroid, 936f 966f, 967f in lipid synthesis, 853, 854f Parkinson disease, protein misfolding in, 150 personalized genomic medicine, 39, 340b, 350–351 phosphatidylglycerol 3-phosphate, in passive transport, 404 pertussis toxin, 443b triacylglycerol synthesis, 853 Pasteur, Louis, 18b, 189, 555, 587 Perutz, Max, 141, 141f phosphatidylinositol(s), 370–371 patch-clamp technique, 421, 421f PFK-1. See phosphofructokinase-1 (PFK-1) membrane distribution of, 388, 388f pattern-regulating genes, 1188–1191 pH, 60–61, 60f, 60t synthesis of, 854f, 855–856, 855f, 856f, 857f Pauling, Linus, 54, 105, 117f, 120, 126, 133, 196 of aqueous solutions, 60–61, 60f, 60t in yeast, 855, 856f

PCNA (proliferating cell nuclear antigen), 1026 of blood, 66–67 phosphatidylinositol 4,5-bisphosphate (PIP2), 363, PCR (polymerase chain reaction), 327–331, 328f buffering and, 63–69, 64f, 65f 364f, 370–371 PDI (protein disulfi de isomerase), in protein enzymatic activity and, 61, 67, 67f, 210f, 212–213 membrane distribution of, 388, 388f folding, 147 functional importance of, 61 in signaling, 370–371 pellagra, 535 in hemoglobin-oxygen binding, 170–171, 170f phosphatidylinositol kinases, 855, 855f, 857f penicillin. See also antibiotics Henderson-Hasselbalch equation for, 64–65 phosphatidylinositol pathway, 447–451, 450f mechanism of action of, 224, 824f isoelectric, 77t, 84 phosphatidylinositol 4-phosphate, membrane plasmids and, 981 determination of, 94, 95f distribution of, 388, 388f

pentose(s), 244, 244s measurement of, 60–61 phosphatidylinositol 3,4,5-trisphosphate (PIP3), in conformations of, 282, 283f neutral, 59 signaling, 370–371, 450f, 456–457 nucleic acid, 282, 283f scale for, 60t phosphatidylserine, 855–856 nucleotide, 244, 244s, 281–284, 282f–284f standard free-energy changes and, 509t in lipid synthesis, 853, 854f, 855–856, 856f ring numbering conventions for, 281f, 284 in titration curve, 62–63, 62f, 63f, 83–84, 83f membrane distribution of, 388, 388f BMInd.indd Page I-30 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-30 Index

phosphoanhydrides, 307f phospholipid head group attachment, 854f of receptor tyrosine kinases, 453–458, phosphocreatine, 520s, 906, 946b, 947s phospholipid head-group exchange reaction, 454f–456f cellular concentration of, 518t 855–856, 857f substrate-level, 553–554 hydrolysis of, 520, 520s phosphomannose isomerase, 563 in sucrose synthesis, 820–821, 821f in muscle contraction, 945f, 947 phosphopantetheine, 84f, 836 in transcription, 1068, 1184

phosphodiester linkages, in nucleic acids, phosphopentose isomerase, 576–577 phosphorylation potential (⌬Gp), 518 284–285, 285f phosphoporin E, structure of, 393f phosphotyrosine-binding domains, 460–462 phosphodiesterase, in vision, 479, 479f phosphoprotein phosphatase 1 (PP1), 621 phosphotyrosine phosphatases (PTPases), 463 phosphoenolpyruvate (PEP), 221s, 554, 554s in glycogen metabolism, 624, 625f photolyases, 536 acetate as source of, 656–657 phosphoprotein phosphatase 2A, 606, 607f DNA, 1028t, 1032–1033, 1034f dehydration of 2-phosphoglycerate to, 554 phosphoproteins, 89t reaction mechanism of, 1034f enolase catalysis of, 220 phosphoramidite method, of DNA synthesis, photon, 771 in gluconeogenesis, 570–572, 570t, 571f, 305, 305f absorbed, energy conversion of, 774–775, 775f 572f, 956 5-phosphoribosyl-1-pyrophosphate (PRPP), 892 photophosphorylation in glyceroneogenesis, 849f, 850 5-phosphoribosylamine, 912 ATP synthesis by, 786–788, 787f, 788f in glyoxylate cycle, in plants, 826f phosphorolysis, 560–561 chemiosmotic theory of, 731 hydrolysis of, 520, 520f of glycogen and starch, 560–561 chloroplasts in, 732 synthesis of, from pyruvate, 570–572, 571f of glycosidic bonds, vs. hydrolysis, 613–614 in cyanobacteria, 789, 789f, 790f transfer of phosphoryl group from, to ADP, phosphorus, covalent bonds of, 515–516, 515f general features of, 769–771 554–555 phosphorus-oxygen bond, 515–516, 515f light absorption in, 771–776, 773f phosphoenolpyruvate carboxykinase, 570, 571s, phosphoryl group oxidative phosphorylation and, 732. See also 610, 611f ATP and, 524 oxidative phosphorylation in triacylglycerol synthesis, 849f, 850, 851f, 944 function of, in glycolysis, 545f stoichiometry of, 787

phosphoenolpyruvate carboxylase, in C4 pathway, in glycolysis, 546–548 photopigments, 480, 480f, 771–776, 773f 815f, 816 phosphoryl group transfer, 515–516, 524f. See also accessory, 772f, 773–774, 774f phosphofructokinase-1 (PFK-1), 549, 593, 594t phosphorylation of Halobacterium salinarum, 789–790 regulation of, 604, 604f, 605f ATP in, 517–527 primary, 771–773, 772f, 773f. See also phosphofructokinase-2 (PFK-2), 606 chemical basis for, 517–519, 518f chlorophyll(s) phosphoglucomutase, 614 from 1,3-bisphosphoglycerate to ADP, 552–554 photorespiration, 812–818, 813f, 814f, 815f

as catalyst in glucose metabolism, 614f from inorganic polyphosphate, 518t, 527 in C4 plants, 815–818, 815f 6-phosphogluconate dehydrogenase, 576 from phosphoenolpyruvate to ADP, 554–555 photosensory neurons, 477, 477f–480f phosphogluconate pathway, 575. See also pentose phosphorylase, 646b photosynthesis, 769–790, 799–812 phosphate pathway phosphorylase a phosphatase, 621 action spectrum for, 774, 774f phosphoglucose isomerase, 549, 594t phosphorylase b kinase, 621 ATP in, 808–812, 808f–811f

phosphoglutamase, 560 phosphorylase kinase, 230 C2 cycle in, 815 2-phosphoglycerate, 221s, 554s phosphorylase phosphatase, 230 in C4 plants, 815–818 conversion of 3-phosphoglycerate to, 554, 554f phosphorylated compounds, free-energy of in CAM plants, 818 dehydration to phosphoenolpyruvate, 554 hydrolysis of, 520, 520f, 521–522, 521f, carbon-assimilation reactions in, 769, 770f, 809, enolase catalysis of, 220, 221f 521t, 522f 810–812, 811f 3-phosphoglycerate, 520s, 552–554, 554s ranking of, 523f carbon dioxide assimilation in, 801–806. See also in amino acid biosynthesis, 892–894, 894f phosphorylation. See also autophosphorylation Calvin cycle conversion of of acetyl-CoA carboxylase, 841, 842f carbon fi xation in, 800, 801–806, 821f. See also to 2-phosphoglycerate, 554 of amino acid residues, 228–231 Calvin cycle to glyceraldehyde 3-phosphate, 801, 803f, of ATPase transporters, 26, 411, 412f electron fl ow in, 769 804, 808f bioenergetics and, 517–527 central photochemical event in, 776–786, in glycolate pathway, 813f, 814 consensus sequences in, 230–231, 232f 777f–782f, 784f, 785f

Pi exchange for, 809–810, 809f, 810f of cyclin-dependent protein kinases, 485–486, dark reactions of, 809 in starch synthesis, 821 485f, 486f, 488f in evolution, 35, 37f, 788–790, 791f synthesis of, 801–804, 803f in DNA repair, 486, 488, 488f exciton transfer in, 774–775 phosphoglycerate kinase, 552–553, 804, 805f in DNA replication, 1013, 1014f in genetically engineered organisms, 815, phosphoglycerate mutase, 554, 594t in enzyme cascades, 434, 434f, 456, 456f 816b–817b reaction of, 554, 554f in enzyme regulation, 228–231, 231t, 232f glycolate pathway in, 813–815, 813f 3-phosphoglyceric acid, 520s of fructose 6-phosphate to fructose 1, light absorption in, 771–776 phosphoglycerides. See glycerophospholipids 6-bisphosphate, 549–550 by photopigments, 771–774, 772f–774f. 2-phosphoglycolate, 812, 813f in gene regulation, 1184 See also photopigments in glycolate pathway, 813–815, 813f, 814f of glucose, 548–549 light-dependent reactions in, 769, 770f phosphohexose isomerase, 549 of glycogen phosphorylase, 229f, 230 NADPH in, 808–812, 808f–811f reaction mechanism of, 549f in heart muscle, 948 photophosphorylation and, 769–770. See also phosphoinositide 3-kinase (PI3K), 456, 456f multiple, 231, 232f photophosphorylation phospholipase, 368, 368f, 378 oxidative, 731–769. See also oxidative photorespiration and, 812–818, 813f, 814f, 815f

phospholipase A phosphorylation Pi-triose antiporter in, 809–810, 810f in eicosanoid synthesis, 846f posttranslational, 1136, 1136f reaction centers in, 774–778, 775f outer membrane, structure of, 393f in protein targeting, 1142, 1143f in bacteria, 776–778, 777f, 778f phospholipase C, 370, 378, 447, 457f proton gradient in, 786–787, 807f Fe-S, 777–778 phospholipid(s), 363. See also lipid(s) respiration-linked, 553–554 integration of, 779–781 head groups of, 363, 852–853, 854f, of retinoblastoma protein, 488, 488f photosynthetic effi ciency and, 778–779 855–856, 857 reversibility of, 231 in plants, 779–781, 779f, 780f lysosomal degradation of, 368, 368f of rhodopsin, 479f, 480 reductive pentose phosphate cycle in, 801 membrane. See membrane lipids in RNA processing, 1085 starch synthesis in, 810, 818–821 synthesis of, 852–859 in signaling, 453–460. See also signaling state transitions in, 783 cytidine nucleotides in, 853, 853f, 854f in bacteria, 473, 473f sucrose synthesis in, 253, 809–810, 819–821, in Escherichia coli, 853–855f, 854f in -adrenergic pathway, 438–446, 439f, 444t 819f, 820f in eukaryotes, 855–856, 855f–857f by -adrenergic receptor kinase, 446 water in, 69 head group attachment in, 852–853, 853f, 854f by cAMP, 446–447 photosynthetic biomass, 257 head-group exchange reaction in, by cGMP, 459–460 photosynthetic carbon reduction cycle, 800 855–856, 857f by G protein–coupled receptor kinases, 446 photosystem I/II, 774, 779–783, 780, 780f, 781f,

salvage pathways in, 856, 857f in IP3/DAG pathway, 447–451, 457f 782f, 784f steps in, 852 in JAK-STAT pathway, 457–458, 457f cytochrome b6 f complex links of, 782–783, 782f in vertebrates, 855–856, 857f multivalent adaptor proteins in, 460–464 integration of, in chloroplasts, 779–783 in yeast, 855, 857f in PI3K-PKB pathway, 456, 456f supramolecular complex of, 781–782, 781f transport of, 857–858 in plants, 474 phototrophs, 4, 5f phospholipid bilayer, 387–389, 387f by protein kinase A, 439f, 442–443, 444t, 446 phycobilin, 773 BMInd.indd Page I-31 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-31

phycobiliprotein, 773 plasma, 950, 950f fuel storage in, 255–256 phycobilisomes, 773, 774f plasma lipoproteins, transport of, 864–871, 867f functions of, 255–257, 262t, 263 phycoerythrobilin, 772s plasma membrane, 3, 3f. See also membrane(s) glycoconjugate, 263–268, 264f

phylloquinone (vitamin K1), 374, 375s, 780 bacterial, 5, 6f heteropolysaccharides, 260–262 phytanic acid, oxidation of, 685–686, 685f composition of, 386–387, 386f, 386t homopolysaccharides, 254–259 phytol, 771 lipid rafts in, 399, 399f hydrolysis of, 257, 558–560, 569f

Pi. See phosphate, inorganic lipopolysaccharides of, 268, 268f molecular size of, 262t pI (isoelectric point), 77t, 84 microdomains of, 398–399, 399f molecular weight of, 255 determination of, 94, 95f neuronal, transport across, 949 repeating unit in, 262t

Pi-triose antiporter, 780f, 809–810 permeability of, 56 structure of, 254–255, 254f, 256f, 257–259, 257f, PI3K-PKB pathway, 456, 456f protein targeting to, 1142, 1143f 258f, 259f, 260f, 262t pigments syndecans in, 264, 264f weak interactions in, 258–259 bile, heme as source of, 904–906, 934f plasma membrane Ca2ϩ pump, 410–411, 411f polysomes, 1135, 1136f in color vision, 480, 480f plasma proteins, 950 polyunsaturated fatty acids (PUFAs), 359 light-absorbing, 771–774, 772f–774f. See also plasmalogens, 364, 365f, 856, 858f Pompe disease, 617t photopigments double bond of, 856, 858f Popják, George, 862, 863f lipids as, 370, 376, 376f synthesis of, 856–857, 858f porins, 393, 733, 733f pili, 6f plasmid(s), 5, 317–319, 981, 982f -barrel structure of, 391, 393, 393f Ping-Pong mechanism, 207, 207f antibiotic resistance–coding, 981 porphobilinogen, 902 pioglitazone (Actos), 852, 852s, 964–965, 970t plasmid vectors, 317–319, 318f, 320f porphyrias, 904, 906b

PIP2. See phosphatidylinositol 4,5-bisphosphate plasmodesmata, 816 porphyrin(s), 158, 902 (PIP2) Plasmodium falciparum, inhibition of, 576b glycine as precursor of, 902–904, 905f PIP3. See (phosphatidylinositol 3,4,5-trisphos- plastids, 800–801, 800f, 801f porphyrin ring, 150f, 158 phate), (PIP3) evolution of, 36 Porter, Rodney, 175 pituitary plastocyanin, 780 porters. See transporter(s)

anterior, 936f, 937, 937f plastoquinone (PQA), 375, 375s, 780 positive-inside rule, 393 posterior, 936f, 937, 937f platelet(s), 233–234, 950, 950f posterior pituitary, 936f, 937 pituitary hormones, 938f platelet-activating factor, 365, 365f postinsertion site, 1014 PKA. See protein kinase A (PKA) synthesis of, 856, 858f posttranslational modifi cations, in protein

pKa (relative strength of acid/base), platelet-derived growth factor receptor, 463 synthesis, 1114–1115, 1115t, 1136–1137. 62, 62f, 63f PLC (phospholipase C), 447 See also protein synthesis of amino acids, 77t, 83–85, 83f–85f plectonemic supercoiling, 992–993, 994f potassium, blood levels of, 950 effects of chemical environment on, 83–84, 84f PLP. See pyridoxal phosphate (PLP) potassium ion channels, 422–424, 422f, 423f, in Henderson-Hasselbalch equation, 64–65 pluripotent stem cells, 1192, 1192f 465–466, 466f of R groups, 77t, 87 poisons ATP-gated, 954 in titration curve, 62–63, 62f, 63f, 83–84, 83f ion channels and, 424–426 defective, diseases caused by, 426t PKB (protein kinase B) translation inhibition by, 1138–1139 in glucose metabolism, 953f, 954 activation of, 456, 456f pol, 1086f, 1087 in signaling, 465–466, 466f, 468 in signaling, 456, 456f frameshifting and, 1111 potassium ion concentration, in cytosol vs. PKC. See protein kinase C (PKC) pol II. See RNA polymerase II and related entries extracellular fl uid, 465t PKD1 (protein kinase D1), 456 Polanyi, Michael, 196 potassium ion transport, NaϩKϩ ATPase in, PKG (protein kinase G), 459–460 polar lipids, transport of, 857–858 411–412, 412f PKU. See phenylketonuria (PKU) polarity potential energy, of proton-motive force, 744 plant(s) of amino acids, 78 PPARs (peroxisome proliferator-activated aquaporins in, 418–419 in embryonic development, 1186–1187 receptors), 679–682, 842, 965–966,

C3, 802 hydrophilicity/hydrophobicity and, 50–53, 50t, 966f, 967f C4, 815–818 51f, 51t, 52f ppGpp (guanosine tetraphosphate), 308, 308s CAM, 818 poly(A) site choice, 1076 PPi (inorganic pyrophosphate), 819–820 carbohydrate metabolism in, 799–812, 825–826, poly(A) tail, 1075, 1075f PPI (peptide prolyl cis-trans isomerase), 826f. See also Calvin cycle polyacrylamide gel electrophoresis (PAGE), 93–94, in protein folding, 147 cell structure in, 7f 93f. See also electrophoresis PPK-1 (polyphosphate kinase-1), 527 cell wall synthesis in, 822–823 polyadenylate polymerase, 1075, 1075f PPK-2 (polyphosphate kinase-2), 527 desaturases in, 843, 843f polycistronic mRNA, 294, 294f Prader-Willi syndrome, 967 DNA in, 983 polyclonal antibodies, 178 pravastatin (Pravachol), 872b ethylene receptor in, 475–476, 475f polyketides, 376 pRb (retinoblastoma protein), 488, 488f genetically engineered, 815, 816b–817b polylinkers, 317, 317f PRDM16, 971 gluconeogenesis in, 819f, 820–821, 820f polymerase chain reaction (PCR), 327–331, 328f pre-replicative complexes (pre-RCs), 1025 glycolate pathway in, 813–815, 813f in DNA genotyping, 329b–330b pre-rRNA, processing of, 1077–1079, 1078f, 1079f glycolysis in, 820–821, 820f quantitative, 331, 331f pre-steady state, 202 immune response in, 475–476, 476f reverse transcriptase, 331 prebiotic chemistry, 33–34 leguminous, symbiotic relationship of polymorphic protein, 97 precipitation, protein, 144 nitrogen-fi xing bacteria and, 887–888, 887f polynucleotide(s), 286 prednisolone, 372, 372s membrane components in, 386t synthetic, in genetic code studies, 1105 prednisone, 372, 372s membrane lipids of, 365, 365f polynucleotide kinase, 315t pregnenolone, 875f metabolite pools in, 826, 826f polynucleotide phosphorylase, 1085, 1105 prehistoric humans, genome sequencing for, mitochondria in, alternative mechanism for polypeptide(s), 86. See also peptide(s) 349–351 NADH oxidation in, 746, 746b–747b size of, 87 preinitiation complex (PIC), 1179 mitochondrial respiration in, 812 vs. proteins, 86 prenylation, 861f NADPH synthesis in, 839 polypeptide chain elongation, in protein synthesis, preproinsulin, 934, 934f organelles in, 800–801, 800f, 801f 1114, 1129–1134. See also protein synthesis, preribosomal rRNA (pre-rRNA), processing of, osmotic pressure in, 57 elongation in 1077–1079, 1078f, 1079f pentose phosphate pathway in, 801, 811–812, polyphosphate, inorganic, 518t, 527, 527s presenilin-1, 348, 349 825–826 as phosphoryl donor, 518t, 527 primary active transport, 405, 409 photorespiration in, 812–818, 813f, 814f, 815f polyphosphate kinase-1 (PPK-1), 527 primary structure, of proteins, 96–108, 97 photosynthesis in. See photosynthesis polyphosphate kinase-2 (PPK-2), 527 primary systemic amyloidosis, 149 reaction centers in, 779–781, 780f polysaccharide(s), 15, 243, 254–263. See also primary transcript, 1069 signaling in, 372–373, 847, 933 carbohydrate(s) splicing of, 1074f vascular, 372–373 in cell communication, 263–268, 264f primases, 1018, 1019t, 1021–1022, 1023t plant glyoxysome, oxidation in, 683, 683f classifi cation of, 254–255, 262t primate, nonhuman, genome of, 345–347, 345f plant peroxisome, oxidation in, 683, 683f conformations of, 258–259, 259f primer plant substances, biosynthesis of, from amino in extracellular matrix, 260 in DNA replication, 1014, 1015f, 1017–1018, 1087 acids, 908, 909f folding of, 257–259, 258f, 259f in RNA replication, 1087 BMInd.indd Page I-32 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-32 Index

primer terminus, 1014, 1015f evolution of, 33–34, 33f, 34f, 140. See also protein catabolism, in cellular respiration, 634f priming, 623, 623f evolution Protein Data Bank (PDB), 115f, 132 of glycogen synthase kinase 3 phosphorylation, 623f evolutionary signifi cance of, 1093 protein disulfi de isomerase (PDI), in protein primosome, 1021 fi brous, 125–130. See also fi brous proteins folding, 147 replication restart, 1041 fl avoproteins, 535–537, 536f, 536t protein domains, 137 prion diseases, 150b–151b folding of. See protein folding microdomains, 398–399 prion protein (PrP), 150b–151b functional classifi cation of, 38–39 protein families, 140 pro-opiomelanocortin (POMC), 934, 934f functions of. See protein function protein folding, 31, 31f, 1114–1115, 1115t. probes, fl uorescent, 448b–449b fusion, 325, 333, 400 See also tertiary structure procarboxypeptidase A, 698 G. See G protein(s) assisted, 146–147, 147f, 148f procarboxypeptidase B, 698 globular, 125, 130–138. See also globular chaperones in, 146–147, 147f, 148f processivity, of DNA polymerases, 1014 proteins chaperonins in, 146, 147, 148f prochiral molecules, 648b as glucose source, 956t, 958 domains and, 137, 137f proenzymes, 232 half-life of, 572, 590t, 1147 energy for, 116–117 progesterone, synthesis of, 874, 874f homologous, 38, 106 errors in, 148–151 programmed cell death, 492–494, 494f immune system, 174–179 in globular proteins, 132f, 133–138 prohormones, 934 inhibitory, in ATP hydrolysis during ischemia, motifs (folds) in, 137–140, 139f–140f proinsulin, 934, 934f 760, 760f patterns in, 138–140, 139f–140f prokaryotes, 3. See also bacteria intrinsically disordered, 141–142, 142f, 769 protein disulfi de isomerase in, 147 proliferating cell nuclear antigen (PCNA), 1026 iron-sulfur, 735 representation of, 132f proline, 79, 79s, 721, 892 Fe-S centers of, 736f rules for, 137–138 in helix, 122 isoelectric point of, 77t, 84 secondary structures in, 133–138, in helix, 122, 123, 124f determination of, 94, 95f 137f–140f, 151b in turns, 123 membrane. See membrane proteins steps in, 144–146, 145f biosynthesis of, 892, 893f misfolded, 148–151 thermodynamics of, 146, 146f in collagen, 127, 127f, 128b–129b in mitochondrial electron-transfer chain, 738t protein function, 75f, 157–184. See also conversion of, to -ketoglutarate, 721, 721f molecular weight of, 87t protein-ligand interactions properties of, 77t, 79 estimation of, 94, 95f amino acid sequence and, 97 proline-rich activation domains, 1182 motor, 179–184, 180f–183f analysis of, 333–337 prolyl 4-hydroxylase, 129b multifunctional, 684 comparative genomics in, 333 promoters, 1060–1061, 1061f, 1067f, 1157–1158 multimeric, 140 DNA microarrays in, 337–338, 337f, 338f expression vectors and, 321, 322f multisubunit, 87, 87t epitope tagging in, 333–334, 335, 335f specifi city factors of, 1157 naming conventions for, 1010 protein tags in, 335 proofreading native, 31, 116 yeast two-hybrid analysis in, 335–337, 336f in transcription, 1015, 1016f, 1060 nuclear, targeting of, 1143–1144, 1144f catalytic. See enzyme(s) in translation, 1121–1122, 1133–1134 oligomeric, 87t, 88, 140 cellular, 332 propionate, 678 orthologous, 38, 106 conformational changes and, 158 Propionibacterium freudenreichii, in overview of, 75 expression patterns and, 333 fermentation, 567 oxygen-binding, 158–174 molecular, 332 propionyl-CoA, 678 paralogous, 38 multiple, 642b–643b oxidation of, 678, 678f phosphoproteins, 89t noncatalytic, 158 propionyl-CoA carboxylase, 678 phosphorylation and dephosphorylation of, 592f phenotypic, 331–332 proplastid, 801 plasma, 950 principles of, 157–158 propranolol, 438s polymorphic, 97 structural correlates of, 115, 125–126, proproteins, 232 polypeptide chains in, 87–88, 87t. See also 130–131, 333 prostaglandin(s), 371, 371f, 845. See also polypeptide(s) protein kinase(s), 229–230. See also specifi c types eicosanoid(s) posttranslational processing of, 1114–1115, AMP-activated, 594 synthesis of, 845, 846f 1115t, 1136–1137 autoinhibition of, 461f, 462

prostaglandin E1, 446, 475s proproteins, 232 -adrenergic receptor, 445f, 446 2ϩ prostaglandin H2, 845, 846f proteolytic activation of, 232f, 235 Ca /calmodulin-dependent, 451–452, 451t prostaglandin H2 synthase, 845 protomeric, 140 cAMP-dependent. See protein kinase A (PKA) prostaglandin inhibitors, 845–847, 846s, 935 RAG, 1050–1051, 1052f in cancer treatment, 490b–491b prosthetic groups, 89, 89t, 190 regulatory. See also gene regulation in cell cycle regulation, 485–488 heme as, 158 DNA-binding domains of, 1160–1163 cGMP-dependent, 459–460 posttranslational addition of, 1137 renaturation of, 144f consensus sequences for, 230–231, 231t protease(s) respiratory, 766t cyclin-dependent, 485–488, 485f, 486f in amino acid sequencing, 99–100, 100t mitochondrial gene encoding of, 766t G protein–coupled, 446 regulation of, 235 ribosomal, 1116t phosphorylation by, 229–230, 456–457, 456f serine, 218–219, 219f synthesis of, rRNA synthesis and, receptorlike, in plants, 476, 476f subclasses of, 218 1170–1171, 1170f in signaling, 444t, 446, 451–452, 451t, 453–460, protease inhibitors, 1088 Rieske iron-sulfur, 735, 741f 460–464, 461f proteasomes, 3, 487, 1147–1148 scaffold, 434, 999, 1000f substrate specifi city of, 231, 231t protein(s), 15, 86. See also gene(s) and specifi c in chromatin, 1000f in transcription, 1068 proteins separation/purifi cation of, 89–96 tyrosine-specifi c, 453–458, 454f–456f allosteric, 166 column chromatography in, 86–92, 90f, 93t epidermal growth factor receptor as, amino acid composition of, 88, 89t. See also dialysis in, 90 456–457, 463 amino acid(s) electrophoresis in, 92–95, 93f–95f insulin receptor as prototype of, 453–457, amphitropic, 390 for enzymes, 93t, 95–96, 95f 454f–456f body stores of, 956t fractionation in, 86–92, 90f platelet-derived growth factor receptor as, bound water molecules in, 54–55, 55f isoelectric focusing in, 94, 95f 456–457, 463 catalytic, 27–28 protocols for, 93t in rafts, 463 cellular concentration of, regulation of. See gene signaling. See signaling proteins protein kinase A (PKA), 438–444 regulation structure of. See protein structure activation of, 438–439, 439f, 440f, 456 conformation of, 115–116 in supramolecular complexes, 9, 10f, 31 AKAPs and, 446–447 conjugated, 89, 89t synthesis of. See protein synthesis in -adrenergic pathway, 438, 439f, 440f, 442–443 crude extract of, 89 transport of. See membrane transport; enzymes/proteins regulated by, 442–443, culling of, 270 transporter(s) 444t, 446 degradation of, 1147–1149 trifunctional, 674 inactivation of, 439–440, 439f, 440f denaturation of, 143–146, 144f uncoupling, 763, 963 measurement of, by FRET, 448b–449b enzyme. See enzyme(s) as universal electron carrier, 532 protein kinase B (PKB) enzyme degradation of, in amino acid catabolism, protein binding. See protein-ligand interactions activation of, 456, 456f 696–699, 698f protein C, 234 in signaling, 456, 456f BMInd.indd Page I-33 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-33

protein kinase C (PKC), 450 codons in, 1105, 1106–1113. See also codons proteostasis, 143, 143f activation of, 371 elongation in, 1114, 1115t, 1129–1134 prothrombin, 375, 376 protein kinase D1 (PKD1), 456 aminoacyl-tRNA binding in, 1128, 1128f, 1130 proto-oncogenes, 489, 489f protein kinase G (PKG), 459–460 direction of, 1127, 1127f protomers, 88, 141

protein-ligand interactions, 157–158 elongation factors in, 1129–1130 proton fl ow, through cytochrome b6 f complex, 782f allosteric, 166, 166f peptide bond formation in, 1130–1132, 1132f proton gradient binding equilibrium in, 160 errors in, 1121–1122 in ATP synthesis, 748–749, 750f, 751–752, 751f binding sites for, 157, 166–167, 175 evolutionary signifi cance of, 1117b conservation of, in mitochondrial electron- complementary, 179–184 fMet-tRNAfMet in, 1127 transfer reactions, 743–745, 744f conformational changes in, 158, 165f, frameshifting in, 1111 in electron fl ow and phosphorylation, 786–787 166–167, 166f inhibition of, 1138–1139 proton hopping, 55, 55f, 58–59, 58f cooperative binding in, 163–169, 166f initiation of, 1114, 1115t, 1127–1129 proton-motive force, 744, 744f enzyme. See enzyme(s) in bacteria, 1127–1128, 1128f active transport and, 757, 757f graphical representations of, 160f in eukaryotes, 1128–1129, 1130f bacterial fl agella rotation by, 766, 766f heterotropic, 166 initiation complex in, 1127–1129, 1128, 1128f, proton pumps. See ATPase(s); transporter(s) homotropic, 166 1130f, 1131t proton transfer, in acid-base catalysis, in immune system, 174–179 initiation factors in, 1131t, 1184 199, 199f induced fi t and, 157 Shine-Dalgarno sequences in, 1127–1128 protoporphyrin, 158, 904 ligand concentration and, 161–162 mRNA degradation in, 1136 PRPP (5-phosphoribosyl-1-pyrophosphate), 892 models of overview of, 1113–1115, 1115t Prusiner, Stanley, 150b MWC (concerted), 167–168, 170f polypeptide release in, 1114, 1115t pseudoinosine, 284s sequential, 167–168, 170f polysomes in, 1135, 1136f pseudouridine, 1080 modulators in, 166 posttranslational modifi cations in, 1115t, psi angle, secondary structures and, of oxygen-binding proteins, 158–174. See also 1136–1137 123–124, 124f hemoglobin-oxygen binding amino acid modifi cations, 1136, 1137f psicose, 246s principles of, 157–158 amino-terminal/carboxyl-terminal PTB domains, 461 protein structure and, 162–163 modifi cation, 1136 PTEN, 456 quantitative descriptions of, 159–162, 167 carbohydrate side chain attachment, puffer fi sh poisoning, 424–426 regulation of, 158 1136–1137 pulsed fi eld gel electrophoresis, 320 reversibility of, 157 isoprenyl group addition, 1137, 1137f in cloning, 320 specifi city of, 157 loss of signal sequences, 1136 pumilio, 1188–1190, 1189f protein moonlighting, 642b–643b prosthetic group addition, 1137 purine(s), 282 protein phosphatases, 230–231 proteolytic processing, 1137 biosynthesis of, 898–899, 903f protein precipitation, 144 proofreading in, 1121–1122, 1133–1134 degradation of, 920–922, 921f protein-protein interactions, analytical techniques protein folding in, 1114–1115, 1115t, ring atoms of, 912f for, 334–337 1136–1137 purine bases. See also base(s), nucleotide/ protein S, 234 rate of, 144–145, 1103 nucleic acid protein sequences. See amino acid sequences; regulation of. See gene regulation anti form of, 290, 290f nucleic acid sequences ribosome as site of, 1103–1104, 1115–1118 Chargaff’s rules for, 288 protein sorting, 1142 ribozyme-catalyzed, 34–35, 34f, 1092–1094, chemical properties of, 286–287 protein structure, 115–151 1117b deamination of, 299–300, 300f helix and, 120f, 121–122, 122f RNA world hypothesis and, 34–35, 34f, hydrogen bonds of, 286–287, 287f amino acid sequences and, 31, 31f, 104 1093–1094 loss of, 300, 300f analysis of, 97–102. See also amino acid rRNA synthesis and, 1170–1171, 1170f nucleic acid, 282–284, 282t, 283s, 284s sequencing steps in, 1113–1115, 1115t nucleotide, 281–284, 282f–284f conformation and, 123–124, 124f termination of, 1114, 1115t, 1134–1135, 1135f recycled, by salvage pathways, 922 classifi cation of, 138–140, 139f–140f thermodynamics of, 1135 structure of, 10s, 281–284, 282f–284f, 282t, covalent, 97–102 transcription coupled with, 1135–1136, 1136f 286–287 database for, 115f, 138–140, 139f–140f transcriptional. See transcription syn form of, 290, 290f free energy of, 116 translational. See translation tautomeric forms of, 286, 286f functional correlates of, 115, 125–126, 130–131, translocation in, 1132–1133, 1133f weak interactions of, 286–287, 287f 143–144, 333 protein tagging, 325–327, 325t purine nucleotides key concepts for, 115 in affi nity chromatography, 325–327, 325t biosynthesis of, 912–922, 913f, 914f ligand binding and, 162–163 epitope, 333–334, 335 regulation of, 914–915, 914f motifs (folds) in, 137–140, 139f–140f. See also glutathione-S-transferase, 326, 326f catabolism of, 920–922, 921f protein folding tandem affi nity purifi cation, 335, 336f puromycin, 1138 nuclear magnetic resonance studies of, protein targeting, 1140 purple bacteria, bacteriorhodopsin in, 391 135b–136b, 135f, 136f to chloroplasts, 1142–1143 pyranoses, 246–247, 248f, 249f oligosaccharides and, 267–268 in endoplasmic reticulum, 1140, 1141f conformations of, 249f overview of, 115–119 glycosylation in, 1141–1143, 1143f pyridine nucleotides, 532, 535 primary, 96–108, 96f, 97 in Golgi complex, 1142, 1143f pyridoxal phosphate (PLP), 699, 718f quaternary, 96f, 125, 140–141. See also lectins in, 272–273 in glycogen phosphorylase reaction, 614 quaternary structure to lysosomes, 1142, 1143f in transfer of -amino groups to -ketoglutarate, Ramachandran plots for, 119f, 120, 124f to mitochondria, 1142–1143 699–700, 699f, 701f representations of, 132f to nucleus, 1143–1144, 1144f pyrimidine(s), 282 secondary, 96f, 119–125, 120f, 122f–124f. See peptide translocation complex in, 1140, 1141f catabolism of, 920–922, 922f also secondary structure to plasma membrane, 1142, 1143f degradation of, 920–922, 922f stability of, 116–117 receptor-mediated endocytosis in, 1146–1147 pyrimidine bases, 282, 282f. See also base(s), supersecondary, 137–140 signal recognition particle in, 1140, 1141f nucleotide/nucleic acid tertiary, 96f, 97, 125–140. See also tertiary transport mechanisms in, 1142–1143, 1143f. See recycled, by salvage pathways, 922 structure also membrane transport pyrimidine dimers three-dimensional, 31, 31f, 115–151 protein turnover, 590 photolyase repair of, 1032–1033, 1034f weak interactions and, 54–55, 56f, 116–117 protein tyrosine kinases. See tyrosine kinases radiation-induced formation of, 300, 301f x-ray diffraction studies of, 131, 134b–135b, proteoglycan aggregates, 266 pyrimidine nucleotides, biosynthesis of, 915–916, 134f–135f proteoglycans, 261, 263–268, 264f 915f, 916f protein superfamilies, 140 proteolysis, 1147–1149, 1147f, 1148f regulation of, 916, 916f protein synthesis, 102–104, 103f, 104t, 1113–1139 ATP-dependent, 1147 pyrophosphatase, inorganic, 524 amino acid activation in, 1113, 1115t, 1119–1123, in protein activation, 232f, 235 in plants vs. animals, 819–820 1120f–1122f ubiquitin-dependent, 1147–1149, 1147f pyrophosphoryl group, ATP and, 524 aminoacyl-tRNA binding sites in, 1128, 1128f proteolytic enzymes, regulation of, 232f, 235 pyrophosphoryl transfer, 524f aminoacyl-tRNA formation in, 1119–1123, proteome, 15, 590 pyrosequencing, 339–341, 341f 1120f–1122f proteomics, 15 pyrrolysine, 1124b BMInd.indd Page I-34 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-34 Index

pyruvate, 516s, 554s, 555 rafts, 399, 399f in signaling, 436–437, 436f alternative fates for, 608, 608f in signaling, 463 tyrosine kinase, 453–457, 456f. See also receptor in amino acid biosynthesis, 895–898, 896f, 897f RAG proteins, 1050–1051, 1052f tyrosine kinases amino acid degradation to, 715–717, 715f, 717t Ramachandran plots, 117, 119, 119f, 124f receptor guanylyl cylases, 437 conversion of, to phosphoenolpyruvate in Ran GTPase, 1144–1145 receptor histidine kinase, 473, 473f gluconeogenesis, 570–572, 570t, rancidity, 361 receptor-ligand binding, 435b 571f, 572f random coil, 119 equilibrium constant for, 435b decarboxylation and dehydrogenation of, Ras, 441b, 455, 456f saturation in, 435b 635–636, 637f binary switches in, 438, 440f, 441b–443b Scatchard analysis for, 421b, 435b fates under anaerobic conditions, 563–568 mutations in, 489 in signaling, 433–434, 434f, 435b in fermentation, 563–568 ras oncogene, 489, 492 receptor-mediated endocytosis, 868–869, 868f, glucogenic amino acids in, 574t rate constant (k), 194 1146–1147, 1146f in gluconeogenesis, 573t, 957f, 958 rate equation, 194, 203, 203f receptor potential, 481 in glyceroneogenesis, 849f, 851f rate-limiting step, 193 receptor tyrosine kinases, 436–437, 453–458 in glycolysis, 545f, 546, 951, 952f, 955, 955f rational drug design, 210 epidermal growth factor receptor as, energy remaining in, 546 Rb gene, 492 456–457, 463 fate of, 548f reaction. See chemical reaction(s) insulin receptor as prototype of, 453–457, hepatic metabolism of, 941f, 942 reaction centers, 774, 775f, 776–778 454f–456f in lactic acid fermentation, 563–565 in bacteria, 776–778, 777f, 778f platelet-derived growth factor receptor as,

oxidation of, to acetyl-CoA and CO2, 634 Fe-S, 777–778 456–457, 463 phosphoenolpyruvate synthesis from, integration of, 779–781 in rafts, 463 570–572, 571f photosynthetic effi ciency and, 778–779 receptorlike kinases, in plants, 476, 476f synthesis of, 941f, 942 in plants, 779–781, 779f, 780f recognition sequences, 315, 315t pyruvate carboxylase, 570, 594t, 650, 652s reaction coordinate diagram, 24f, 26, recombinant DNA, 314 biotin in, 570, 571f, 651–653, 652f, 653f 192–193, 193f recombinant DNA technology, 314–339 reaction mechanism of, 652f reaction equilibria, 192–194 affi nity chromatography in, 91f, 92, 93t, pyruvate decarboxylase, 565, 568t reaction intermediates, 193 325–327, 327t pyruvate dehydrogenase, 568t, 635 reaction mechanisms, 216–217, 216f–217f, applications of pyruvate dehydrogenase complex, 634 See also specifi c enzymes legal, 329b–330b acetyl-CoA produced by, 654–655, 654f reactive oxygen species (ROS), 740, 745–746, 745f medical, 39, 339–342, 340b, 347–351 coenzymes of, 634–635, 635f hypoxia and, 760–761, 761f cloned gene expression in, 321–325 in decarboxylation and dehydrogenation of reading frame, 1105, 1105f cloning and, 314–325. See also cloning pyruvate, 635–636, 652f frameshifting and, 1111 DNA genotyping in, 329b–330b enzymes of, 635–636 open, 1107 DNA libraries in, 332, 332f, 335f reaction catalyzed by, 634f RecA, 319, 322, 322f, 324, 1040–1041, 1041f DNA microarrays in, 337–338, 337f, 338f structure of, 636f in SOS response, 1169–1170 enzymes used in, 314–317, 315t pyruvate kinase, 554, 594t RecBCD helicase/nuclease, 1040–1041, 1040f expression vectors in, 321 ATP inhibition of, 606–608, 607f receptor(s). See also specifi c types fusion proteins in, 333–334 regulation of, 955 acetylcholine. See acetylcholine receptor genome sequencing in, 333, 339–351

pyruvate phosphate dikinase, in C4 pathway, adhesion, 436f, 437 immunofl uorescence in, 333–334, 334f 815f, 817 affi nity for, 433–434, 434f immunoprecipitation in, 335, 335f

PYY3-36, 962f, 967, 968 ANF, 459 linkage analysis in, 347–349 -adrenergic, 438–446 oligonucleotide-directed mutagenesis in, desensitization of, 445–446, 445f 324–325 Q in rafts, 463 polymerase chain reaction in, 327–331 Q (coenzyme Q), 735, 735s structure of, 438, 439f protein purifi cation in, 335 Q (mass-action ratio), 509, 593, 760 defi nition of, 175 protein tagging in, 325–327, 327t, 333–335, in carbohydrate metabolism, 593, 593t desensitization of, 434, 434, 434f, 445–446 335f, 336f Q cycle, 741, 741f epidermal growth factor, 463 pulsed fi eld gel electrophoresis in, 320 quadruplex DNA, 292 erythropoietin, 457–458, 457f restriction endonucleases in, 314–317, 315t quantitative PCR (qPCR), 331, 331f ethylene, 475–476, 475f site-directed mutagenesis in, 323–324 quantum, 771 Fas, 493, 493f yeast two-hybrid analysis in, 336–337, 336f, 337f quaternary protein structure, 96f, 97, 125, G protein–coupled. See G protein–coupled recombinant gene expression, hosts for, 140–141 receptor(s) 322–323, 324f of -keratin, 126, 126f ghrelin, 962f recombinase, 1046–1047, 1047f quinolones, 992b–993b glycine, 424 recombination. See DNA recombination guanylin, 460 recombination signal sequences, 1050–1051, 1052f hormone, 436f, 437, 932–933, 1183–1184, 1183f recombinational DNA repair, 1039–1041, 1044f R insulin, 453–457, 454f–456f recoverin, 480 R (gas constant), 507t LDL, 867 red-anomalous trichromats, 480 R groups, 76, 77t, 78–81 leptin, 961, 963 red blood cells. See erythrocytes aromatic, 77t, 79–80, 79f neurotransmitter, 468 redϪ dichromats, 480 ionization behavior of, 87 nicotinic acetylcholine, 424 red muscle, 944–945 negatively charged (acidic), 77t, 79f, 81 defective, 426t redox pair. See conjugate redox pair nonpolar aliphatic, 77t, 78–81, 79f open/closed conformation of, 468, 469f redox reactions. See oxidation-reduction reactions

pKa of, 77t, 87 in signaling, 467–468, 469f reducing end, 252 polar uncharged, 77t, 79f, 80–81 synaptic aggregation of, 398 reducing equivalent, 530, 735 positively charged (basic), 77t, 79f, 81 nuclear, 437 reducing sugars, 251, 252–253 R-state, in hemoglobin-oxygen binding, 163–165, olfactory, 481 reduction potential 165f, 171–172, 172f peroxisome proliferator-activated, 965–966, 966f and affi nity for electrons, 530–531, 530f, 531t

R2C2 complex of protein kinase, 439–440, 440f platelet-derived growth factor, 463 standard. See standard reduction potential racemic mixture, 17 rhodopsin, 477, 480 reductive pentose phosphate cycle, 801 Racker, Efraim, 750, 750f as signal amplifi er, 933 reductive pentose phosphate pathway, 579 radiation steroid (nuclear), 436f, 437 Refsum disease, 686 electromagnetic, 771, 771f sweet taste, 481 regulated gene expression, 1156 ionizing, DNA damage from, 300 T-cell, 175 regulators of G protein signaling, 442b ultraviolet, absorption of, by DNA, 297–298 receptor agonists, 438 regulatory cascade, 232 chemical changes due to, 300, 301f receptor antagonists, 438 regulatory enzymes, 226–235 radicals, 512 receptor channels, ligand-gated. See ligand-gated allosteric, 226–228, 228f, 2271 free, 514–515, 515f receptor channels complex, 235 radioimmunoassay (RIA), 930–932 receptor enzymes, 436–437, 436f, 453–460 covalent modifi cation of, 226, 229–232, 229f, Raf-1, 455, 456f guanylyl cyclase, 459–460, 459f 231t, 232f BMInd.indd Page I-35 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-35

functions of, 226–227 retinoblastoma protein (pRb), 488, 488f ribulose 1,5-bisphosphate, 801, 808, 808f kinetics of, 227–228, 228f retinoic acid, 373, 374s, 936 oxygen incorporation in, 812–813, 813f proteolytic cleavage and, 231–232, 232f retinoid hormones, 933t, 936 regeneration of, 805–806, 806f–808f, 808 unique properties of, 226 retinoid X receptors (RXRs), 871, 871f ribulose 1,5-bisphosphate carboxylase/oxygenase regulatory proteins. See also gene regulation and retinol (vitamin A), 373–374, 374s, 936 (rubisco), 802–804. See also rubisco specifi c proteins, e.g., promoters retrohoming, 1089, 1090f ribulose 5-phosphate, 577s, 806, 806f–808f DNA-binding domains of, 1160–1163 retrotransposons, 1088–1089 ribulose 5-phosphate kinase, light activation of, regulatory sequences, 980, 980f retroviruses, 1086f, 1087–1089 811, 811f regulons, 1166 evolutionary signifi cance of, 1088–1089 Richardson, Jane, 137

relative molecular mass (Mr), 14b HIV as, 218–219, 1088, 1088f ricin, 1139 relaxed-state DNA, 985 oncogenic, 1088, 1088f rickets, 373, 373f release factors, 1114, 1134–1135, 1135f reverse cholesterol transport, 867f, 869, Rieske iron-sulfur protein, 735, 741f Relenza, 271 873–874, 874f rifampicin, 1068 renaturation, of proteins, 143–146, 144f reverse transcriptase, 315t, 1086–1087, 1086f Rinaldo, Piero, 724b repetitive DNA, 984 HIV, 1088, 1088f RNA, 15. See also nucleic acids replication, 977. See also DNA replication; RNA reverse transcriptase PCR, 331 base pairs in, 287, 287f, 294–295, 295f, 296f replication reversible inhibition, 207–208, 208f, 209f catalytic, 34–35, 34f, 1069, 1070–1075, origin-independent restart of, 1041 reversible terminator sequencing, 1082–1085, 1082f–1084f, 1092–1094, 1117b replication factor A (RFA), 1026 341–342, 342f in cis/trans, 1171–1173 replication factor C (RFC), 1026 Rezulin (troglitazone), 970t degradation of, reverse transcriptase in, replication fork, 1012, 1013f, 1021–1023 RF-1, 1134, 1135f 1086–1087 in bacteria, 1012, 1013f, 1021–1023, 1021f, 1022f RF-2, 1134, 1135f development, SELEX method in, 1093, in eukaryotes, 1026 RFA (replication factor A), 1026 1095b, 1117b stalled, 1024–1025, 1024f RFC (replication factor C), 1026 early studies of, 293–294 damage from, 1034–1035, 1036f rhamnose, 249s editing of, 1075–1076, 1111–1113 repair of, 1039–1041, 1044f. See also DNA Rhodobacter sphaeroides, 776 in evolution, 34–35, 34f repair Rhodopseudomonas viridis, 776 5Ј cap of, 1070 replication origin photoreaction center of, 778f functions of, 293–294 in bacteria, 1012 rhodopsin, 463, 478f, 479f, 480 guide, 1111 in eukaryotes, 1025 absorption spectra of, 480, 480f hairpin loops in, 1065f, 1084–1085 replication restart primosome, 1041 activation of, 477 hydrolysis of, 285, 285f replicative forms, 981 phosphorylation of, 479f, 480 messenger. See mRNA (messenger RNA) replicative transposition, 1049, 1050f structure of, 478f micro, 1081, 1185 replicators, 1025 rhodopsin kinase, 480 noncoding, 1186 replisomes, 1017, 1023 ribofuranose, 282, 283f nucleotides of, 282t, 283–284, 283f. See also reporter construct, 334 ribonuclease nucleotide(s) reporter gene, 334 denaturation of, 143–146, 144f parasitic, 1094 repressible gene products, 1156 renaturation of, 143–146, 144f phosphodiester linkages in, 284–285, 285f repression, 1156 structure of, 133t posttranslational processing of. See RNA repressors, 1061, 1157, 1158f ribonucleic acid (RNA). See RNA processing in eukaryotic gene regulation, 1170–1171, 1180, ribonucleoproteins, small nuclear, preribosomal, processing of, 1077–1079, 1184–1185 1072–1073 1078f, 1079f Lac, 1061, 1162, 1166 ribonucleoside 2Ј,3Ј-cyclic monophosphates, 284 as primordial catalyst, 34–35, 34f DNA-binding motif of, 1162, 1163f ribonucleoside 3Ј-monophosphates, 284 rate of turnover of, 1070 SOS response and, 1169–1170 ribonucleotide(s), 282t, 283, 283f. See also ribosomal. See rRNA (ribosomal RNA) transcription activators as, 1180 nucleotide(s) SELEX analysis of, 1093, 1095b, 1117b translational, 1170–1171, 1170f, 1184–1185, as precursors of deoxyribonucleotides, 917–920, self-replicating, 34–35, 34f, 1092–1094 1188 917f, 918f small, 1171–1173 Reshef, Lea, 850 reduction of, 917–918, 917f small nuclear, 1073, 1081, 1097b respirasomes, 743 ribonucleotide reductase, 917, 917f small nucleolar, 1079, 1080f, 1081, respiration, 633 proposed mechanism of, 918, 918f 1097b, 1186 alternative pathways of, in plants, 746b–747b regulation of, 918–920 small temporal, 1185 bicarbonate buffer system in, 66–67 ribose, 10s, 244s, 246s splicing of, 1069–1075, 1070f, cellular, 633 conformations of, 282 1072f–1074f. See also splicing stages in, 633, 634f ribose 5-phosphate, 806, 806f, 807f structure of, 294–296, 294f–296f mitochondrial electron transfer in, 732–747. ribose 5-phosphate isomerase, 806f synthesis of, 294, 1058–1069. See also See also electron-transfer reactions, ribose phosphate pyrophosphokinase, 892 transcription mitochondrial ribosomal (r) proteins, 1116t, 1170–1171, 1170f transfer. See tRNA (transfer RNA) respiratory chain, mitochondrial, 732–747, 734. synthesis of, rRNA synthesis and, 1170–1171, translation of, 31f See also electron-transfer reactions, 1170f TUF, 1097b mitochondrial ribosomal RNA. See rRNA (ribosomal RNA) weak interactions in, 286–287, 287f, respiratory proteins ribosomes, 3, 1115–1118 294–295 mitochondrial genes encoding, 766t aminoacyl-tRNA binding sites on, RNA aptamers, 1095b response coeffi cient (R), 598–599, 599b 1128, 1128f RNA-dependent polymerases, 1085–1094, response elements, 589 bacterial, 6f, 1115–1117, 1116f 1086f, 1092 response regulator, 473 discovery of, 1103–1104 RNA-DNA hybrids, denaturation of, 298 restriction endonucleases, 314–317, 315f, eukaryotic, 7f, 1116f, 1117–1118 RNA enzymes, 1069, 1069, 1070–1075, 1082–1085, 315t, 317f recycling of, 1135 1082f–1084f, 1092–1094, 1117b recognition sequences for, 315, 315t as site of protein synthesis, 1103–1104, RNA world hypothesis and, 34–35, 34f, type I, 314–315 1115–1118 1093–1094 type II, 315, 315t structure of, 1115–1118, 1116f self-replicating, 1092–1094 type III, 314–315 subunits of, 1115–1117, 1116f, 1117 RNA interference (RNAi), 1185–1186, 1185f restriction-modifi cation system, 302, 314 synthesis of, rRNA synthesis and, RNA polymerase(s), 1019t reticulocytes, translational regulation in, 1170–1171, 1170f DNA-dependent, 1058–1060, 1058f, 1184–1185 riboswitches, 1172–1173 1156–1157 retinal, 16s, 373–374, 374s, 477, 480 ribothymidine, 283f promoter binding of, 1060–1061, 1063f 11-cis-retinal, 16s, 477, 480 ribozymes, 1069, 1069, 1070–1075, 1082–1085, RNA-dependent, 1092 all-trans-retinal, 16s 1082f–1084f, 1092–1094, 1117b subunit of, 1060–1061, 1061f, 1157 retinal cones, 477–480, 477f, 478f, 480f RNA world hypothesis and, 34–35, 34f, specifi city factors in, 1157 in color vision, 480 1093–1094 in transcription, 1058–1060, 1058f, 1156–1157 retinal rods, 477–480, 477f–479f self-replicating, 1092–1094 in bacteria, 1058–1060, 1058f retinoblastoma, 492 ribulose, 246s in eukaryotes, 1064–1068, 1065f, 1066t, 1067f BMInd.indd Page I-36 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-36 Index

RNA polymerase holoenzyme, 1060, 1060f catalytic activity of representations of, 132f

RNA polymerase I, 1064 with CO2 substrate, 802–804, 803f, 804f supersecondary, 137–140, 139f–140f. See also RNA polymerase II, 1064–1068, 1065f with oxygen substrate, 812–813, 813f protein folding carboxyl-terminal domain of, 1064, 1067f evolutionary signifi cance of, 812–813 secondary systemic amyloidosis, 149 promoter binding of, 1177–1178 genetically engineered, 815, 817b secretin, 697–698 regulation of, 1068 in photorespiration, 812–813 sedoheptulose 1,7-bisphosphatase, 811, 811f, 817b structure of, 1064, 1067f reaction mechanism, 830f sedoheptulose 1,7-bisphosphate, in Calvin cycle, TATA box and, 1064, 1065f regulation of, 804, 811–812 806, 806f, 807f transcription factors and, 1066, 1067f structure of, 802, 802f sedoheptulose 7-phosphate, in Calvin cycle, 806f RNA polymerase III, 1064 rubisco activase, 804 seed germination RNA processing, 1069–1085 Ruv proteins, 1041, 1042f gluconeogenesis in, 825–826 in bacteria, 1069–1070, 1077–1080, 1078f triacylglycerols in, 683, 683f differential, 1075–1077, 1076f segment polarity genes, 1188, 1190 editing in, 1075–1076, 1111–1113 S segmentation genes, 1188 enzymatic, 1069, 1070–1075, 1082–1085, S. See entropy (S) selectable markers, 318 1082f–1084f SAA protein, 149 selectins, 270–272, 283f, 402 in eukaryotes, 1070, 1070f, 1075–1077, 1076f, saccharides. See carbohydrate(s); sugar(s) selenocysteine, 81, 82s 1079, 1079f Saccharomyces cerevisiae. See also yeast SELEX, 1093, 1095b, 1117b 5Ј cap in, 1070 recombinant gene expression in, 323 self-splicing introns, 1070–1071, 1093 of miRNA, 1081, 1081f Sakmann, Bert, 421, 421f enzymatic properties of, 1082–1085, 1084f of mRNA, 1069–1077 salicylate, 845–846, 846s evolutionary signifi cance of, 1093 polyadenylate polymerase in, 1075, 1075f Salmonella typhimurium, 1173f semiconservative replication, 1011 poly(A) site choice in, 1076 gene regulation in, 1173–1174 sensory neurons poly(A) tail addition in, 1075, 1075f lipopolysaccharides of, 268, 268f gustatory, 481, 482f polynucleotide phosphorylase in, 1085 salts, dissolution of, 50–52, 51f olfactory, 481, 482f rate of, 1084 salvage pathways, 856, 857f, 910–911, 922 visual, 477–480, 477f–480f ribozymes in, 1069, 1070–1075, 1082–1085, Samuelsson, Bengt, 371, 371f sequential feedback inhibition, 900 1082f–1084f Sandhoff disease, 369b sequential model, of protein-ligand binding, of rRNA, 1077–1079 Sanger, Frederick, 97, 98, 302 167–168, 170f of snoRNA, 1081 Sanger sequencing, 302–304, 303f sequential reactions, in gluconeogenesis, 573t of snRNA, 1081 sarcomere, of muscle fi ber, 181, 181f, 182 SERCA pump, 410–411 splicing in, 1069–1075, 1070f, 1072f–1074f sarcoplasmic reticulum, of muscle fi ber, serine, 10s, 79s, 81, 715, 894 alternative patterns of, 1075–1077, 1076f 181, 181f biosynthesis of, 892–894, 894f RNA replicase, 1092 satellite DNA, 984 chymotrypsin acylation/deacylation of, 218 RNA replication, 1085–1094, 1086f saxitoxin, 424–426 in chymotrypsin mechanism, 218 evolutionary signifi cance of, 34–35, 34f, scaffold, chromosomal, 999, 1000f degradation of, to pyruvate, 715, 715f, 716f 1092–1094, 1117b scaffold proteins, 434, 462, 463f in glycolate pathway, 813–815, 813f, 814f homing in, 1089, 1090f AKAPs as, 447f in lipid synthesis, 853, 854f introns in, 1088–1089, 1090f in chromatin, 1000f phosphorylated, 230–231 retrotransposons in, 1088–1089, 1088f in enzyme regulation, 463f binding domains for, 460–464, 461f reverse transcriptase in, 1085–1086, 1086f Scatchard analysis, 435b, 932 in plants, 475–476, 476f RNA replicase in, 1092 SCDs (stearoyl-ACP desaturases), 843 properties of, 77t, 81 self-generated, 34–35, 34f obesity and, 843 in proteoglycans, 264, 264f telomerases in, 1089–1092, 1091f Schally, Andrew, 930 serine dehydratase, 715 RNA transcripts SCK test, 708b reaction mechanism of, 715f complex, 1076–1077, 1076f, 1077f SCOP database, 138–140 serine hydroxymethyltransferase, 715, 849 primary, 1069 scramblases, 396f, 397 reaction mechanism of, 715f splicing in, 1074f scrapie, 150b serine proteases, 218–219, 219f processing of. See RNA processing screenable markers, 318, 319 serotonin, 475s, 909 of unknown function, 1097b scurvy, 128b–129b receptor for, as ion channel, 424 RNA viruses, 1088, 1088f, 1092 SDS. See sodium dodecyl sulfate (SDS) serpentine receptors. See G protein–coupled RNA world hypothesis, 34–35, 34f, SecA/B chaperones, 1145–1146, 1145f receptor(s) 1093–1094 second messengers, 437–452, 482–484. See also serum albumin, 669–670, 943 RNase P, 295f, 1078f, 1082, 1083 signaling; signaling proteins serum amyloid A (SAA), 149 Roberts, Richard, 1070 calcium as, 450f, 451–452, 451f, 451t 7 transmembrane segment receptors. See G rod cells, 477–480, 477f–479f cAMP as, 446–447 protein–coupled receptor(s) Rodbell, Martin, 441b, 441f in -adrenergic pathway, 438–440, sex hormones, 372, 372s, 475s, 933t, 935 ROS (reactive oxygen species), 740 439f, 440f steroid, 372, 372s rosettes, in cellulose, 822, 822f diacylglycerol as, 447–451, 457f synthesis of, 874, 874f rosiglitazone (Avandia), 852, 852s, G protein–coupled receptors and, 437–452 SGOT test, 708b 964–965, 970t in gene regulation, 1171 SGPT test, 708b

Rossmann fold, 534, 534f IP3 as, 447–451, 457f SH2 domain, 454, 457f, 458, 461, 461f rotational catalysis, 752–755 mechanism of action of, 446–447 Shafrir, Eleazar, 850 in ATP synthesis, 730f, 755f, 756f nucleotide, 308, 308f Sharp, Phillip, 1070 Rous, F. Peyton, 1088 secondary active transport, 405, 409 shellfi sh poisoning, 424–426 Rous sarcoma virus, 1088, 1088f secondary metabolites, 15 Shine, John, 1127 rRNA (ribosomal RNA), 282, 1057, 1115–1118, secondary structure(s), 96f, 97, 119–125, 120f, Shine-Dalgarno sequence, 1127–1128 1116t. See also RNA 122f–124f shivering thermogenesis, 948 preribosomal, processing of, 1077–1079, helix as, 120–122, 120f, 122f, 123t, Shoemaker, James, 724b 1078f, 1079f 124f, 125f short tandem repeats (STRs), in DNA genotyping, processing of, 1077–1079 amino acids in, 123–124, 124f 329b–330b structure of, 1115–1118, 1116t, 1118f conformation as, 122f–125f, 123–125, 126t shotgun method, in mass spectrometry, 379, 379f synthesis of, protein synthesis and, 1170–1171, turn as, 123, 124f, 126t shotgun sequencing, 341–342 1170f bond angles in, 123–124, 124f shuttle vectors, 320 RS system of stereochemical nomenelature, 18, 78 of fi brous proteins, 120–125, 120f, sialic acid, 249s, 250, 269–270, 366s RU486, 471, 472s 122f–124f, 126t in gangliosides, 366, 366s rubisco, 802–804 of globular proteins, 133–138, 133t, 137f–140f sickle cell disease, 172–174, 173f activation of, 804, 810–812 motifs in, 137–140, 139f–140f. See also protein sickle cell trait, 173

in C3 plants, 815 folding subunit, of RNA polymerase, 1060–1061, 1061f in C4 plants, 815–818, 815f in protein folding, 133–138, 137f–140f, 151b signal recognition particle (SRP), 1140, 1141f in CAM plants, 818 Ramachandran plots for, 120, 124f signal sequence(s), 1140 BMInd.indd Page I-37 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-37

of insulin, 934 tyrosine kinases in, 453–458, 456f snRNA (small nuclear RNA), 1073, 1081, 1097b, posttranslational removal of, 1136 in vision, 477–480, 477f–479f 1186 in protein targeting, 1140 signaling cascade, 933 snRNPs (small nuclear ribonucleoproteins), in bacteria, 1144–1146 signaling pathways 1072–1073 in eukaryotes, 1140, 1144–1146 -adrenergic, 438–446, 439f, 440f, 444f, 445f sodium, blood levels of, 950 signal transduction, 433, 436f. See also signaling conservation of, 482–483, 483f sodium dodecyl sulfate (SDS), 94

signaling, 433–494 IP3/DAG, 447–451, 450f in electrophoresis, 94, 95f acetylcholine receptor in, 467–468, 469f JAK-STAT, 457–458, 457f, 962–963, 963f sodium-glucose symporter, 417 adaptor proteins in, 446, 460–464 phosphatidylinositol, 447–451, 457f sodium ion(s), 533s adhesion receptors in, 436f PI3K-PKB, 456, 456f dehydrogenase reactions and, 532–535, adrenergic receptors in, 438–446 signaling proteins, 460–464 533f, 534t autoinhibition in, 461f, 462 binding domains of, 456–457, 460–464 sodium ion channels, 424 autophosphorylation in, 453–454. See also examples of, 462f defective, diseases caused by, 426t autophosphorylation IRS-1, 454, 456f in signaling, 465–467, 466f, 467f, 468 in bacteria, 473, 473f, 474t multiple, 460–464, 462f sodium ion concentration, in cytosol vs. basic mechanisms of, 436–437, 436f PTB, 461 extracellular fl uid, 465t -adrenergic response in, termination of, SH2, 454, 461f sodium ion transport, NaϩKϩ ATPase in, 444–445 specifi city of, 460, 461f 411–412, 412f blood in, 949–950 conservation of, 482–483, 483f solar energy, 769, 770f carbohydrates in, 283f interaction of, 460–464 solenoidal supercoiling, 993, 994f, 996 caveolae in, 399, 400f multivalent, 460–464, 462f solubility cooperativity in, 434, 434f signaling systems of amphipathic compounds, 52–53, 52f, 53f cross talk in, 458 common features of, 482–484, 483f entropy and, 51, 53, 53f eicosanoids in, 847 self-inactivation of, 483–484 of gases, 51, 51t enzyme cascades in, 434, 434f, 456, 456f signature sequences, 107, 107f of hydrophilic compounds, 51, 51f in plants, 475–476, 475f, 476f sildenafi l (Viagra), 459, 460s of hydrophobic compounds, 51, 51t in epinephrine regulation, 438–446, 439f silent mutations, 1027, 1111 solutes evolutionary aspects of, 457, 482–483 silk fi broin, 130, 131f concentration of, colligative properties and, fatty acids in, 847 simple diffusion, 403, 403f, 404f 55, 55f G protein–coupled receptors in, 436f, 437, simple-sequence DNA (repeats), 344, 984 membrane transport of. See membrane transport 438–446 simple transposition, 1049, 1050f solutions gated ion channels in, 424, 436f, 437, 464f, simvastatin (Zocor), 872b buffered, 63–69, 64f, 65f 465–467, 466f single nucleotide polymorphisms (SNPs), colligative properties of, 55–56, 55f, 56f in gene regulation, in eukaryotes, 1182–1184 344–345, 345f hypertonic, 56–57, 56f guanylyl cyclase in, 445–446, 476f in linkage analysis, 347–349, 348f hypotonic, 56–57, 56f in gustation, 481, 482f, 483f single particle tracking, 398 ionic interactions in, 50–51 hormonal, 930, 930f, 932f, 933 single-stranded DNA-binding protein (SSB), isotonic, 56–57, 56f in hormonal cascade, 937, 938f 1019t, 1020, 1023t osmolarity of, 56–57, 56f signal amplifi cation in, 937 in mismatch repair, 1029–1030, 1031f pH of, 60–61, 60f, 60t target tissues in, 936–937, 937f siRNA (small interfering RNA), 1185 solvation layer, 116 insulin in, 453–457, 454f–456f, 934, 934f sirtuin, 142f. See also histone deacetylases solvents in insulin regulation, 453–457, 454f–456f sister chromatids, 994, 1042–1044, 1043f boiling points of, 48t integration in, 434, 434f, 468 sitagliptin (Januvia), 970t heat of vaporization of, 48t lipids in, 371–372 site-directed mutagenesis, 323–324 melting points of, 48t in mammals, 474t site-specifi c recombination, 1038, 1046–1049, organic, in lipid extraction, 377–378 membrane polarization in, 464–467, 1047f water as, 50, 51f. See also water 464f, 466f sitosterol dextrin, in cellulose synthesis, 822–823 somatostatin, 953 membrane potential in, 464–465, 464f 6-4 photoproduct, 300, 301f sorafenib, 491b membrane rafts in, 463 size-exclusion chromatography, 91f, 92, 93t sorbose, 245, 246s neuronal, 930, 930f skeletal muscle. See muscle Sos, 443, 454–455, 456f in olfaction, 481, 482f, 483f skin cancer, in xeroderma pigmentosum, SOS response, 1035, 1036t, 1169–1170, 1169f overview of, 433–437 1037b–1038b Sp1, glutamine-rich domains of, 1181–1182, 1182f phosphatidylinositol in, 855, 855f Skou, Jens, 411, 411f space-fi lling model, 16, 16f phosphorylation in, 454f–456f, 456 Slack, Rodger, 816 specifi c acid-base catalysis, 199 in plants, 372–373, 473–475, 474f–476f, 474t, sleeping sickness, 211b–212b specifi c activity, 95 847, 933 slow-twitch muscle, 944 specifi c linking difference, 988 protein interactions in, 460–464. See also Sly, William, 724b specifi city signaling proteins small G proteins, 455 enzyme, 197

protein kinases in. See protein kinase(s) small interfering RNA (siRNA), 1185 specifi city constant (kcat/Km), 205, 205t proteoglycans/oligosaccharides in, 263–268, small intestine, fat absorption in, 668–669, 668f specifi city factors, 1157 269–273 small nuclear ribonucleoproteins (snRNPs), spectrin, 398f in proteolysis, 1148 1072–1073 spectrophotometry, 80b receptor desensitization in, 434, 434f, small nuclear RNA (snRNA), 173, 1081, spermidine, 909 445–446, 456f 1097b, 1186 biosynthesis of, 911f receptor enzymes in, 436–437, 436f, 453–460 small nucleolar RNA (snoRNA), 1079, 1081 spermine, 909 receptor-ligand binding in, 433–434, 434f, 435b small RNA (sRNA), 1172–1173 biosynthesis of, 911f second messengers in, 446–452, 482–484. See small temporal RNA (stRNA), 1185 sphinganine, 857, 859f also second messengers SMC proteins, 1000, 1001f sphingolipids, 264, 363f, 365f, 366–368, 367f, 368f signal amplifi cation in, 434, 434f, 443–444, smell, signaling in, 481, 482f in blood groups, 367, 368f 457, 933, 938f Smith, Hamilton, 315 functions of, 367–368

signal-receptor affi nity in, 433–434, 434f SN1 reaction, 220–222, 223f lysosomal degradation of, 368, 368f signal transduction in, 434f, 436f SN2 reaction, 222, 223f membrane distribution of, 389f signal variety in, 436t snake venom, 426 membrane microdomains of, 398–399, 399f specifi city in, 433, 434f SNAP25, 401, 401f structure of, 366s, 367s steps in, 466f SNAREs, 401, 401f synthesis of, 857, 859f steroid hormones in, 372, 372s snoRNA (small nucleolar RNA), 1079, 1080f, transport of, 857–858 steroid receptors in, 436f, 437 1081, 1097b sphingomyelin(s), 366, 367f, 367s, 857, 859f termination of, 456 snoRNPs, 1079 in cell regulation, 371 two-component systems in SNPs (single nucleotide polymorphisms), membrane distribution of, 388, 389f in bacteria, 473, 473f 344–345, 345f sphingomyelinase, in Niemann-Pick disease, 369b in plants, 475–476, 475f, 476f in linkage analysis, 347–349, 348f spliceosomal introns, 1072, 1074f BMInd.indd Page I-38 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-38 Index

spliceosomes, 1072, 1074f stem cells, 1191–1193, 1192, 1192f, 1193f sugar(s), 243. See also carbohydrate(s); splicing, 1069–1070, 1070–1075, 1070f, adult, 1192 monosaccharides; oligosaccharides; 1072f–1074f embryonic, 1192 polysaccharide(s) alternative, 1075–1077 multipotent, 1192 acidic, 249s alternative patterns of, 1050f, 1076f, 1077f pluripotent, 1192, 1192f amino, 249s guanosine in, 1071, 1072f totipotent, 1192, 1192f complex, 243 internal guide sequence in, 1082, 1084f stereochemistry, 16–19, 16f–18f deoxy, 249s spongiform encephalopathies, 150b–151b nomenclature for, 18 dolichols and, 375 squalene stereoisomers, 16, 16f, 76–77, 78 epimers, 245, 246f in cholesterol synthesis, 860f, 861–862, 863f nomenclature for, 18 nonreducing, 252, 253 squalene 2,3-epoxide, 862, 863f optical activity of, 18, 77 nucleotide, 819 squalene monooxygenase, 862, 863f sugar, 243 phosphorylation of, 251 Src, 454, 458 stereospecifi city, 16, 19, 19f, 20f reducing, 251, 252–253 SREBP cleavage-activating protein (SCAP), 870 steroid hormone(s), 372, 372f, 372s, simple, 243 SREBPs (sterol regulatory element–binding 933t, 935 stereoisomers of, 243 proteins), 610, 870, 870f in signaling, 372 sugar code, 269–273, 273f sRNA, (small RNA), 1171–1173 synthesis of, 763–764, 874, 874f, 875f sugar nucleotides, 615–619 SRP (signal recognition particle), 1140 cytochrome P-450 in, 763–764 formation of, 615–616, 618f SSB. See single-stranded DNA-binding protein steroid hormone receptors, 436f, 437, 933, in glycogen synthesis, 617–619, 618f, 620f (SSB) 1183–1184, 1183f suicide inactivators, 210, 211b–212b stability genes, 492 sterol(s), 368–370, 368f sulfation, in proteoglycans, 265, 265f, 266f Stahl, Franklin, 1011 as lipid anchors, 394, 394f sulfolipids, 365, 365f standard free-energy change (Gº), 25, 192, 193f membrane, 386t sulfonylurea drugs, 954, 970, 970t for acid anhydride, 509t microdomains of, 398–399, 399f Sumner, James, 190, 190f additive, 510–511 steroid hormones from, 372, 372s sunitinib, 491b of amide, 509t structure of, 368–370, 368f supercoiled DNA. See DNA, supercoiling of for ATP synthesis, 750–751 sterol regulatory element–binding proteins superhelical density, of DNA, 988 biochemical, 192 (SREBPs), 610, 870–871, 870f superoxide dismutase, 745 concentration dependent, 509–510 sticky ends, 316, 317f superoxide radical, 740 calculation of, 508 stimulatory G protein (Gs), 438, 439f mitochondrial production and disposal of, 745f related to equilibrium constant, 507–508, 508t, adenylyl cyclase and, 438 suppressor tRNA, 1134b 509t self-inactivation of, 438 supramolecular complexes, 9, 10f, 31 units of, 507t stomach ulcers, 271f, 272 Sutent, 491b in electron transfer, 743–745 stop codons, 1107, 1107f. See also codons Sutherland, Earl, 616, 621 equilibrium constant and, 194, 194t, 507–508, storage lipids, 363f sweetness, 254b–255b 508t, 509t classifi cation of, 363f SWI/SNF, in chromatin remodeling, 1175, of peptides, 509t fatty acids, 357–362 1176t, 1180 pH and, 509t waxes, 362, 362f switches, binary, in G protein(s), 438, 440f, vs. free-energy change, 509–510. See also Streptomyces lividans, potassium channel in, 441b–443b free-energy change (⌬G) 422–424, 422f SWR1 family, in chromatin remodeling, 1175, 1176t standard reduction potential (EЊ), 530 streptomycin, 1138, 1139s symbiont, 882 of biologically important half-reactions, 531t stress, oxidative, mitochondria in, symporters, 409, 409f in calculating free-energy change, 531–532 745–746, 745f Naϩ-glucose, 417, 417f measurement of, 530, 530f stress response synaptic transmission, steps in, 466f values for, 531, 531t cortisol in, 958–959, 959t syndecans, 264, 264f, 265 standard transformed constants, 507 epinephrine in, 958, 959t syndrome X, 969–971 starch, 255, 255–259, 262t. See also stringent factor, 1171, 1171f synteny, 333, 333f carbohydrate(s); polysaccharide(s) stringent response, 1171, 1171f synthase, 646b in amyloplasts, 800, 800f stRNA (small temporal RNA), 1185 synthetase, 646b biosynthesis of, 818–821 stroma, 770 system, 21 degradation of, 560–561 Strong, Frank, 535 closed, 21 glucose storage in, 253, 255–256 strong acids, 61–62 isolated, 21 granular form of, 256 Structural Classifi cation of Proteins (SCOP), open, 21 hydrolysis of, 257 138–140, 139f–140f systems biology, 29, 313 structure of, 254f, 255, 256f, 258–259, 258f, substitution mutations, 1027 259f, 260f substrate synthesis of, in plants, 810 enzyme, 158, 192. See also enzyme-substrate T starch phosphorylase, 560 complex T cell(s) (lymphocytes), 175, 175t, 950 starch synthase, 819 substrate channeling, 636–637 antigen binding by, 175 starvation, overproduction of ketone bodies substrate cycle, 601 cytotoxic, 175, 175t during, 688 succinate, 129s, 645 functions of, 175 state transitions, in photosynthesis, 783 conversion of succinyl-CoA to, 644–645, 645f helper, 175, 175t statin drugs, 872b–873b, 873 in glyoxylate cycle, in plants, 826 T-cell receptors, 175 STATs, 457–458, 457f, 963. See also JAK-STAT oxidation of, to fumarate, 646–647 T loop, 1091, 1091f pathway succinate dehydrogenase, 646, 738t, 740. See also t-SNAREs, 401, 401f leptin and, 962–963, 963f Complex II T-state, in hemoglobin-oxygen binding, 163–165, steady state, 202 succinic thiokinase, 645 165f, 171–172, 172f

cellular maintenance of, 589 succinyl-CoA T3 (triiodothyronine), 933t, 936 dynamic, 21 conversion of, to succinate, 644–645, 645f T4 (thyroxine), 933t, 936 steady-state assumption, 202 glucogenic amino acids and, 574t TAG. See triacylglycerol(s) steady-state kinetics, 202 oxidation of -ketoglutarate to, 644 Tagamet (cimetidine), 909 enzyme, 203–205 succinyl-CoA synthase, 645 tagatose, 246s steady-state reactions, 25 reaction of, 645f tags. See protein tagging stearate sucrose, 243, 253, 253f, 819s talose, 246s desaturation of, 842–843, 842f in photosynthesis, 253, 809–810 Tamifl u, 271 synthesis of, 842f synthesis of, in germinating seeds, tamoxifen, 471 stearic acid, 358t 825–826, 826f tandem affi nity purifi cation (TAP) tags, 335, 336f 1-stearoyl, 2-linoleoyl, 3-palimitoyl glycerol, sucrose 6-phosphate, 819, 819s, 837f tandem mass spectrometry (MS/MS), 101, 102f, 360s sucrose 6-phosphate phosphatase, 819, 837f 274, 275f stearoyl-ACP desaturase (SCD), 843 sucrose 6-phosphate synthase, 819, 837f Tangier disease, 874 stearoyl-CoA, 842 sucrose synthase, in cellulose synthesis, 824f Tarceva, 491b BMInd.indd Page I-39 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-39

Tarui disease, 617t thin-layer chromatography, 377f, 378 transaldolase, 577–579, 579, 579s taste thioesters, 635 in Calvin cycle, 806f signaling in, 481, 482f, 483f free-energy of hydrolysis of, 521, 521f covalent interactions with, 579f sweet, 254b–255b thiolase, 674 transaminase, 699 TATA-binding protein (TPB), 1066t, 1068, 1179 thioredoxin, 811, 811f, 917 transamination, 699 TATA box, 1064, 1065f thioredoxin reductase, 917 enzyme-catalyzed, 699f Tatum, Edward L., 642b, 979, 980f 4-thiouridine, 284s transcript taurocholic acid, 370s 30 nm fi ber, 998, 1035f complex, 1076–1077, 1076f, 1077f Tay-Sachs disease, 369b Thompson, Leonard, 931b primary, 1069 TCA (tricarboxylic acid) cycle, 633. See also citric Thomson, James, 1193, 1193f splicing in, 1074f acid cycle 3Ј end, 285, 285f processing of. See RNA processing telomerase, 1089–1092, 1090–1091, 1091f 3Јn5Ј exonuclease activity, in DNA polymerases, transcription, 31f, 294, 977, 1057, 1058–1069. telomeres, 984–985, 985t, 1026, 1089–1092, 1091f 1017, 1017f See also protein synthesis Temin, Howard, 1087, 1087f threonine, 79s, 81, 717, 722, 898 in bacteria, 1003f, 1058–1064, 1058f temperature, absolute, units of, 507t biosynthesis of, 896f, 897–898 regulation of, 1165–1175. See also gene template strand conversion of, to succinyl-CoA, 722, 722f regulation in replication, DNA as, 1011, 1013, 1014f degradation of, to pyruvate, 715f, 717–718 vs. eukaryotes, 1175 in transcription, 1059, 1059f, 1085 phosphorylated, 230–231 defi nition of, 294 Ter sequences, 1023–1025, 1024f binding domains for, 460–464 DNA-dependent, 1058–1069 terminal complexes, in cellulose, 822 in plants, 475–476, 476f DNA supercoiling in, 1058f, 1059f terminal tags, in affi nity chromatography, properties of, 77t drug inhibition of, 1068, 1069f 325–327, 325t threose, 246s enzymology of, 1069. See also ribozymes terminal transferase, 315t thrombin, 233, 265f error rate in, 1060 termination codons, 1107. See also codons thrombomodulin, 234 in eukaryotes, 1064–1068 termination factors, 1134–1135, 1135f thromboxane(s), 234, 371–372, 371f. See also regulation of, 1176–1195. See also gene terminators, transcriptional, 1063–1064, 1065f eicosanoid(s) regulation termites, cellulose digestion by, 257, 257f synthesis of, 846f, 847 vs. bacteria, 1175 tertiary protein structure, 96f, 97, 125–140. See thromboxane synthase, 846f, 847 evolutionary signifi cance of, 1092–1094 also protein folding Thudichum, Johann, 367, 367f initiation of, 1058f, 1059, 1060–1061, 1063f, of fi brous proteins, 126–130. See also fi brous thylakoid(s), 770 1067f, 1068 proteins proton and electron circuits in, 775f of introns, 1070 of globular proteins, 125, 133–138. See also thylakoid membrane nucleoside triphosphate in, 524 globular proteins galactolipids in, 365, 365f phosphorylation in, 1184 of -keratin, 126–127, 126f photosystems in, 775f promoters in, 1060–1061, 1063f, 1067f, Ramachandran plots for, 120, 124f thymidylate, biosynthesis of, 920, 920f 1157–1158 representations of, 132f as chemotherapy target, 924f proofreading in, 1015, 1016f, 1060 testis, 937f thymidylate synthase, 920 proteins in, 1066t, 1068 testosterone, 372f, 372s, 935 reaction mechanism of, 924f rate of, 589, 1059, 1157 tetracosanoic acid, 358t thymine, 10s, 282, 282t, 283f. See also pyrimidine regulation of, 1061–1063, 1155–1195. See also tetracyclines, 1138, 1138s. See also antibiotics bases gene(s) tetradecanoic acid, 358t evolutionary signifi cance of, 299–300 in bacteria, 1165–1175 tetrahydrobiopterin, 714 from 5-methylcytosine deamination, in eukaryotes, 1176–1195 in phenylalanine hydroxylase reaction, 299–300, 300f RNA-dependent, 1085–1094 720, 720f thyroglobulin, 936 steps in, 1066–1068, 1067f

tetrahydrofolate (H4 folate), 712, 712f thyroid, 937f strand elongation in, 1059, 1059f, 1063f, substrate binding to, 195f thyroid hormones, 933t, 936 1067f, 1068 Tetrahymena thermophila, splicing in, thyrotropin, 269 termination of, 1063–1064, 1065f, 1071–1072, 1082, 1083f thyrotropin-releasing hormone 1067f, 1068 tetraplex DNA, 292 isolation and purifi cation of, 930 transcription factors in, 1064–1068, 1067f tetrasaccharide bridge, 264 structure of, 932f translation coupled with, 1135–1136, 1136f

tetrodotoxin, 424–426 thyroxine (T4), 933t, 936 vs. replication, 1058 tetroses, 244 tissue damage, assays for, 708b transcription activators, 1178, 1181–1182, TFIIA, 1066t, 1068, 1179 tissue factor, 233 1182f TFIIB, 1066t, 1068, 1179, 1180 tissue factor protein inhibitor, 234 as repressors, 1180 TFIID, 1180 tissue fractionation, 8, 8f transcription bubble, 1058, 1058f TFIIE, 1066t, 1068, 1179 titins, 182 transcription factors, 589, 1064–1068, 1066t, TFIIF, 1066t, 1068, 1179 titration curves 1067f, 1178–1179 TFIIH, 1066t, 1068 for amino acids, 82–85, 83f, 85f basal, 1178 thermodynamics Henderson-Hasselbalch equation for, 64–65 general, 1066, 1066t, 1067f bioenergetics and, 21–28, 506–527 of peptides, 87 transcriptional attenuation, 1166f–1168f, biological energy transformations and, for weak acids, 62–63, 62f, 63f 1167–1169 506–507, 507t TLS polymerases, 1034–1037, 1038b transcriptional regulation. See gene regulation fi rst law of, 21 TNF. See tumor necrosis factor (TNF) transcriptome, 590, 1057 free energy in. See free energy (G) tocopherols, 374–375, 375s transdeamination, 701 physical constants used in, 507t topoisomerase(s), 989–990, 990f, 991f, 999, 1017, transducin, 478, 479f of protein folding, 146, 146f 1019t, 1020 transfection, 323, 324f second law of, 507 in replication initiation, 1019t, 1020 transfer RNA. See tRNA (transfer RNA) thermogenesis, 944. See also brown topoisomerase inhibitors, 992b–993b transferrin, 642b adipose tissue topoisomers, 989, 990, 990f transferrin receptor, 642b mitochondrial, 762–763 topology, 986 transformation, in cloning, 318 shivering, 948 of DNA, 986 transition mutations, 1111 thermogenin, 763, 944, 962 topotecan (Hycamtin), 992s, 993b transition state thiamine pyrophosphate, 565 totipotent stem cells, 1192, 1192f in enzymatic reactions, 27, 193, 195–197, 217 in Calvin cycle, 805, 807f toxins transition-state analogs, 210 in fermentation, 567f, 568t ion channels and, 424–426 transition-state complementarity, 217 reaction mechanism of, 567f translation inhibition by, 1138–1139 transketolase, 568t, 579, 579s thiazolidinediones, 852, 852s TPB (TATA-binding protein), 1179 in Calvin cycle, 805, 806f, 807f thick fi laments, 180–181, 180f, 181f TC arm, of tRNA, 1118, 1119f covalent interactions with, 579f in muscle contraction, 182–183, 183f trace elements, 12, 12f defect of, Wernicke-Korsakoff syndrome thin fi laments, 180f, 181, 181f trans confi guration, of peptide bonds, 124f exacerbation due to, 580 in muscle contraction, 182–183, 183f trans fatty acids, 361, 362t reactions catalyzed by, 577, 579f BMInd.indd Page I-40 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-40 Index

translation, 31f, 977, 1104. See also protein trichromats, 480 turnover number, 205, 205t synthesis trifunctional protein (TFP), 674 Tus-Ter complex, 1023–1025, 1024f in gene regulation, 1170–1171, 1170f triglycerides. See triacylglycerol(s) 26S proteasome, 1147

regulation of, 1184–1186, 1184f triiodothyronine (T3), 933t, 936 twist (Tw), 989, 989f repression of, 1170, 1170f, 1184–1186, 1188 trimeric G proteins, 438 twisted sheet, 137–138, 137f transcription coupled with, 1135–1136, 1136f trimethoprim, 924s, 925 two-component signaling systems, 473 translational frameshift, 1111 triose kinase, 562 in bacteria, 473, 473f translocation triose phosphate(s) in plants, 475, 475f, 476f in protein synthesis, 1132–1133, 1133f antiporter for, 809–810, 810f two-dimensional electrophoresis, 94, 95f in protein targeting, 1140, 1141f in Calvin cycle, 805–810 type 1 diabetes. See diabetes mellitus, type 1 transmembrane electrical potential. See membrane regeneration of ribulose 1, 5-bisphosphate type 2 diabetes. See diabetes mellitus, type 2 potential from, 805–806, 806f, 807f type I topoisomerases, 990, 991f transpeptidase reaction, 224f synthesis of, 805f, 808–809, 808f type II topoisomerases, 990, 991f, 1021f -lactam antibiotics and, 224, 225f conversion of, to sucrose/starch, tyrosine, 10s, 79–80, 79s, 717, 898 transphosphorylation, between nucleotides, 819–821, 820f biosynthesis of, 898, 902f 526–527, 526f interconversion of, 550, 552f catabolic pathways for, 718f, 719f transport. See membrane transport; protein movement of, 809–810, 810f, 826, 826f insulin receptor and, 453–457 targeting; transporter(s) triose phosphate isomerase, 550, 594t light absorption by, 80f transport vesicles, 400–401, 401f trioses, 244, 244f phosphorylated, 230–231 in lipid targeting, 857–858 triphosphates, nucleoside, nucleoside binding domains for, 460–464, 461f in protein targeting, 1142, 1143f monophosphate conversion to, 916 in cell cycle regulation, 484, 486f transporter(s), 404–409 triple helix properties of, 77t, 79–80 ABC, 413–414 of collagen, 124f, 126t, 127–130, 127f, tyrosine kinases, 456–457 active, 405 128b–129b membrane-protein, 456–457 ATP in, 525–526, 757 of DNA, 292, 293f receptor, 453–458 primary, 405 triplet nucleotides. See codons epidermal growth factor receptor as, 456, secondary, 405 triplex DNA, 292, 293f 457, 463 acyl-carnitine/carnitine, 671 trisaccharide bridge, 264f insulin receptor as prototype of, 453–457, alanine, 703, 703f trisomy, 1045b 454f–456f Ca2ϩ pump, 410–411, 411f tRNA (transfer RNA), 282, 1057, 1079–1080. platelet-derived growth factor receptor as, citrate, 840 See also RNA 456, 457, 463 in cotransport systems, 409, 409f amino acid arm of, 1118, 1119f in rafts, 463 F-type ATPase, 412–413, 413f aminoacylation of, 1119–1123, 1120f–1122f receptor-like, 456–457 fatty acid, 670–672, 670f, 671f anticodon arm of, 1118, 1119f soluble, 457–458 glucose. See glucose transporters base pairing of, with mRNA, 1109–1110, 1110f tyrosine residues, in membrane proteins, glutamine, 702–703, 702f in codon-anticodon pairing, 1109–1110 393, 393f lactose, 416, 416f, 416t, 417f D arm of, 1118, 1119f multidrug, 413–414 functions of, 294 Naϩ-glucose symporter, 417, 417f nomenclature for, 1106 U NaϩKϩ ATPase, 411–412, 412f processing of, 296f, 1079–1080, 1080f UAS (upstream activator sequence), 1178 P-type ATPase, 410–411, 411f recognition of, 1122–1123, 1122f ubiquinone, 375, 375s, 735, 735s passive, 404 structure of, 296f, 1118, 1119f ubiquinone:cytochrome c oxidoreductase, 738t, SERCA pump, 410–411 suppressors, 1134b 740–742, 741f. See also Complex III types of, 425t TC arm of, 1118, 1119f ubiquitin, 487 vs. ion channels, 404, 404f, 421. See also ion in translation, 1104, 1108b–1109b in disease, 1148–1149 channels yeast alanine, 1118, 1119f in protein degradation, 1147–1149, 1147f transposition, 1038–1039, 1049, 1049f troglitazone (Rezulin), 970t ubiquitin cascade, 1147–1148, 1147f in bacteria, 1049, 1049f tropic hormones, 937 defects in, 1148–1149 direct (simple), 1049, 1050f tropins, 937 UBS proteases, 149 in eukaryotes, 1049, 1088–1089, 1088f tropomyosin, 183 ubx, 1191 replicative, 1049, 1050f troponin, 183 UDP (uridine diphosphate), 562 transposons (transposable elements), 344, 984, trp operon, transcriptional attenuation in, UDP-glucose, 615s, 620s, 819s 1049, 1049f 1167–1169, 1167f in cellulose synthesis, 822 bacterial, 1049 Trp repressor, 1167, 1167f in glycogen synthesis, 615–619, 618f, 620f complex, 1049 Trp residues, in membrane proteins, 393, 393f in sucrose synthesis, 819–820 eukaryotic, 1049, 1088–1089, 1088f Trypanosoma brucei rhodesiense, UDP-glucose pyrophosphorylase, 617–618 evolutionary signifi cance of, 1088–1089 211b–212b ulcers, gastric, 271f, 272 trehalose, 253, 253f trypanosomiasis, African, 211b–212b ultrabithorax, 1191 triacontanoylpalmitate, 362f trypsin, 698 ultraviolet radiation absorption triacylglycerol(s), 359f, 360–361, 360f, 362t, 683. synthesis of, proteolytic cleavage in, chemical changes due to, 300, 301f See also fatty acid(s) 231–232, 232f by DNA, 297–298 absorption of, 668–669, 668f trypsin inhibitor, pancreatic, 698 by proteins, 80b, 80f body stores of, 956t trypsinogen, 231–232, 232f, 698 UMP (uridine 5Ј-monophosphate), 283s fate of, 939 tryptophan, 79–80, 79s, 535s, 715, UMUC, in DNA repair, 1035–1037 food sources of, 361 717, 898 UmuD, in DNA repair, 1035–1037, 1036t functions of, 360–361 biosynthesis of, 898, 900f uncompetitive inhibitor, 208, 208f, mixed, 360, 360f degradation of 209f, 209t recycling of, 849–850, 850f, 851, 944 to acetyl-CoA, 717–719, 718f, 719f uncoupling protein 1, 763, 963 in seed germination, 683, 683f to pyruvate, 715, 715f undefi ned coil, 119 simple, 360 light absorption by, 80f underwinding, of DNA, 987, 987f storage forms of, 360–361, 360f properties of, 77t, 79–80 unfolded protein response, 149 stored, mobilization of, 669–670, 670f, 671f, tryptophan synthase, 898 uniporters, 409, 409 943–944 reaction mechanism of, 898, 901f unipotent stem cells, 1192 synthesis of, 848–850, 943–944 tubocurarine, 426 units, of molecular mass, 14b glyceroneogenesis in, 849f, 850–852, 851f TUF RNA, 1096b–1097b universe, 21 hormonal regulation of, 849–850, 850f tumor(s). See also cancer upstream activator sequences (UASs), 1178 triacylglycerol cycle, 850, 850f, 851, 944 solid, glycolysis in, 555, 556b–557b uracil, 10s, 282, 282t, 283f. See also pyrimidine triacylglycerol lipase, 944 tumor necrosis factor (TNF) bases tricarboxylic acid (TCA) cycle, 633. See also citric in apoptosis, 492–494, 494f from cytosine deamination, 299, 300f acid cycle tumor suppressor genes, 489–494, 493f in disease, 920 Trichonympha, 257, 257f tunicamycin, 1141, 1141s tautomeric forms of, 286, 286f BMInd.indd Page I-41 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

Index I-41

uracil DNA glycosylase, 1030–1031 DNA polymerases of, 1026–1027 nonpolar gas solubility in, 51, 51t urate oxidase, 921 lectins and, 273f ordered, 52f, 53, 53f urea, 706 RNA, 1092 in photosynthesis, 69 from amino acid metabolism, 942 oncogenic, 1088, 1088f polarity of, 50 in pyrimidine degradation, 921 selectins and, 270–271 in proteins, 54–55, 55f urea cycle, 704, 705f virusoid, 1083 proton hopping in, 55, 58–59, 58f citric acid cycle links to, 706–708, 707f visible light as reactant, 69 genetic defects in, 709–710 as electromagnetic radiation, 771 solvation layer of, 116 regulation of, 708, 709f photopigment absorption of, 771–774, 772f–774f. as solvent, 50–53, 51f. See also aqueous synthesis in See also photopigments solutions energetic cost of, 708–709 vision weak acids/bases in, 61–63 enzymatic steps in, 704–706, 705f, 706f color, 480, 480f water-splitting complex, 784–785, 785, 785f ureotelic species, 704 signaling in, 477–480, 477f–479f Watson, James D., 97, 287, 287f, 288–289, 339, uric acid vitamin(s), 373–375 977, 1011 excess, 922–923 biotin. See biotin waxes in purine degradation, 921 isoprenoids in beeswax, 362, 362f uricotelic species, 704 as lipid anchors, 394, 394f in carnauba wax, 362 uridine, 283s synthesis of, 874–875, 875f in lanolin, 362 uridine 5Ј-monophosphate (UMP), 283s niacin, 535, 535s weak acids, 61–63. See also acid(s) uridine diphosphate (UDP), 562. See also dietary defi ciency of, 535 as buffers, 63–69, 65f UDP entries pyridoxal phosphate. See pyridoxal phosphate dissociation constants (Ka) of, 61f–63f, 62–63 uridylate, 282t, 283s (PLP) relative strength of. See pKa uridylylation, enzyme, 229f in pyruvate dehydrogenase complex. See pyru- titration curve for, 62–63, 62f, 63f uridylyltransferase, 889 vate dehydrogenase complex Henderson-Hasselbalch equation for, 64–65 uronic acid, 250 tetrahydrofolate. See tetrahydrofolate (H4 folate) weak bases, 61. See also base(s) in glycosaminoglycans, 260–261, 261f vitamin A (retinol), 373–374, 374s as buffers, 63–69 UvrA, in DNA repair, 1032, 1036t vitamin B12 (cobalamin), 678, 680b–681b dissociation constants of, 61f–63f UvrB, in DNA repair, 1032, 1036t defi ciency of, 681, 713–714 weak interactions, 9 UvrC, in DNA repair, 1032 reaction mechanism of, 681f in aqueous solutions, 47–58 UvrD, in DNA repair, 1032 vitamin C (ascorbic acid), 128b–129b binding energy of, 54 defi ciency of, 128b–129b cumulative effect of, 54 functions of, 128b in DNA, 286–287, 287f, 288, 289f, 290f V vitamin D, 933t effects of, on structure and function, 54–55 V segment, of kappa light chain, 1050–1051, 1051f as hormone, 933t, 935 in enzyme-substrate complexes, 53f, 54, v-SNAREs, 401, 401f vitamin D2 (ergocalciferol), 373, 373f 195–197, 196f V-type ATPases, 412. See also ATPase(s) vitamin D3 (cholecalciferol), 373, 373f, 373s hydrogen bonds as, 47–50, 48f–51f, 54–55, 54t, vaccine, viral, 1088 vitamin E (tocopherol), 373, 375s 55f. See also hydrogen bonds vacuoles, 6, 7f vitamin K, 374, 375s hydrophobic, 53, 54t Vagelos, P. Roy, 873b vitamin K1 (phylloquinone), 374, 375s in amphipathic compounds, 52–53, 52f valine, 79, 79s, 722, 898 vitamin K2 (menaquinone), 374 in globular proteins, 132, 132f biosynthesis of, 897–898, 897f VLDL (very-low-density lipoprotein), 865f, 865t, protein stability and, 116–117 catabolic pathways for, 674, 675f, 722f, 723f 866–867 ionic, 9, 54, 54t conversion of, to succinyl-CoA, 722, 722f Vm (membrane potential), 403, 403, 403f, in solutions, 50–51 properties of, 77t, 79 464–465, 464f in macromolecules, 54–55, 55f valinomycin, 418, 418f in signaling, 464–469, 464f of membrane proteins, 390–391, 493f van der Waals interactions, 9, 53, 53t, 117 Vmax (maximum velocity), 201–205, 201f of nucleotide/nucleic acid bases, 286–287 as dipole-dipole interactions, 117 voltage-gated ion channels, 421, 422–424. See also in polysaccharides, 258–259 in myoglobin, 132, 132f ion channels protein stability and, 116–117 tertiary protein structure and, 132, 132f in signaling, 424, 436f, 464–469, 464f, in RNA, 286–287, 287f, 294–295 van der Waals radius, 53, 53t 465–467, 466f in solutions, 53 vanadate, 410, 410s von Euler-Chelpin, Hans, 544 stability of, 54 vane, John, 371, 371f von Gierke disease, 617t system energy and, 54 van’t Hoff equation, 56 von Mering, Josef, 931b tertiary protein structure and, 132, 132f van’t Hoff factor, 56 van der Waals interactions as, 53, 53t, 54t vaporization, heat of weight, regulation of, 849–850, 960–968 of common solvents, 48t W adiponectin in, 964–965, 964f of water, 47, 48–49, 48t Walker, John, 752, 752f ghrelin in, 962f, 966–967, 967f Varmus, Harold, 1088 Warburg, Otto, 554–558, 555 hypothalamus in, 961–962, 961f vascular endothelial growth factor receptor, 490b Warburg effect, 555 insulin in, 963–964, 964f vascular plants, 372–373 warfarin, 234, 375, 375s leptin in, 961–964, 961f–964f vasopressin, 938f waste treatment, anammox bacteria in, 884b–885b peroxisome proliferator-activated vectorial reactions, in oxidative water, 47–70 receptors in, 965–966 phosphorylation, 738 adaptation to life in, 69–70 PYY3-36 in, 962f, 967, 968 vectors. See cloning vectors boiling point of, 47, 48t thermogenesis in, 960 venom, ion channels and, 424–426 electrostatic interactions and, 50, 51f Weizmann, Chaim, 567–568 Venter, J. Craig, 339, 339f evaporation of, 48–49, 48t Wernicke-Korsakoff syndrome, exacerbation of, vertebrate, small, aerobic metabolism of, 564b heat of vaporization of, 47, 48–49 transketolase defect and, 580 very-low-density lipoprotein (VLDL), 865f, 865t, hydrogen bonds in, 47–50, 48f–50f, 55f Western blot, 179 866–867 hydrophilic (polar) compounds and, 50–52, 50t white adipose tissue (WAT), 943, 943f vesicle, 388 hydrophobic (nonpolar) compounds and, 9, 50, white blood cells, 950, 950f Viagra (sildenafi l), 459, 460s 50–53, 50t white muscle, 944–945 Victoria, Queen, 234, 235f ionic interactions in, 50–51, 51f whooping cough, 443b vimentin, 182 ionization of, 58–61 wild-type cells, 33 viral DNA, 980–981, 982t equilibrium constant for, 59 Wilkins, Maurice, 288, 288f viral genome, 980–981, 982t ion product of, 59 Withers, Stephen, 222 viral infections product of, 60 wobble hypothesis, 1110 cancer-causing, 489, 489f, 1088 melting point of, 47, 48–49, 48t Woese, Carl, 105, 1092, 1092f vaccines for, 1088 membrane permeability for, 56 Woolley, D. Wayne, 535 viral oncogenes, 489, 489f membrane transport of, 418–420, 419t, 434 writhe (Wr), 989, 989f viruses. See also retroviruses metabolic, 69 Wurtz, Charles-Adolphe, 192 DNA, 980–981, 1026–1027 molecular structure of, 47–48, 48f Wyman, Jeffries, 167 BMInd.indd Page I-42 25/10/12 1:06 PM user-F408 /Users/user-F408/Desktop

I-42 Index

yeast two-hybrid analysis, 335–337, 336f X Y yellow fl uorescent protein (YFP), X-linked adrenoleukodystrophy (XALD), 683 Yalow, Rosalyn, 930 448b–449b x-ray diffraction studies yeast Young, William, 548, 548f of DNA, 288, 290f centromeres in, 984, 984f of protein structure, 129–130, 131, 134b–135b, chromosomes in, 981 134f–135f DNA of, 981, 982t xanthine, from adenine deamination, 300f fermentation by, 565, 566 Z xanthine oxidase, 921 genome of, 981, 982t, 984f Z disk, 181, 181f, 183f allopurinol inhibition of, 923, 923f membrane components in, 386t Z-DNA, 291, 291f xanthophyll, 774s plasmid vectors from, 320–321, 321f Z scheme, 780 xenobiotics, 763–764 recombinant gene expression in, 323 Zamecnik, Paul, 1104, 1104f, 1115 xeroderma pigmentosum, 1037b–1308b ribosome of, 1116f, 1117–1118 zanamivir, 271 xylose, 219–220, 220s, 246s telomeres in, 984–985, 984f Zellweger syndrome, 682 xylulose, 246s yeast alanine-tRNA, 1118, 1119f zinc fi nger, 1162–1163, 1164f xylulose 5-phosphate, 577s yeast artifi cial chromosomes (YACs), 320–321, Zuckerkandl, Emile, 105 in Calvin cycle, 806, 806f, 807f 321f, 985 zwitterion, 81, 83, 83f in regulation of carbohydrate and fat, 606 yeast replicators, 1025 zymogens, 232–235, 232f, 233f, 697, 699 BEP.indd Page 1 15/10/12 11:27 AM user-F408 /Users/user-F408/Desktop

Abbreviations for Amino Acids

A Ala Alanine N Asn Asparagine B Asx Asparagine or P Pro Proline aspartate Q Gln Glutamine C Cys Cysteine R Arg Arginine D Asp Aspartate S Ser Serine E Glu Glutamate T Thr Threonine F Phe Phenylalanine V Val Valine G Gly Glycine W Trp Tryptophan H His Histidine X — Unknown or I Ile Isoleucine nonstandard amino acid K Lys Lysine Y Tyr Tyrosine L Leu Leucine Z Glx Glutamine or M Met Methionine glutamate

Asx and Glx are used in describing the results of amino acid analytical procedures in which Asp and Glu are not readily distinguished from their amide counterparts, Asn and Gln.

The Standard Genetic Code

UUU Phe UCU Ser UAU Tyr UGU Cys UUC Phe UCC Ser UAC Tyr UGC Cys UUA Leu UCA Ser UAA Stop UGA Stop UUG Leu UCG Ser UAG Stop UGG Trp CUU Leu CCU Pro CAU His CGU Arg CUC Leu CCC Pro CAC His CGC Arg CUA Leu CCA Pro CAA Gln CGA Arg CUG Leu CCG Pro CAG Gln CGG Arg AUU Ile ACU Thr AAU Asn AGU Ser AUC Ile ACC Thr AAC Asn AGC Ser AUA Ile ACA Thr AAA Lys AGA Arg AUG Met* ACG Thr AAG Lys AGG Arg GUU Val GCU Ala GAU Asp GGU Gly GUC Val GCC Ala GAC Asp GGC Gly GUA Val GCA Ala GAA Glu GGA Gly GUG Val GCG Ala GAG Glu GGG Gly

*AUG also serves as the initiation codon in protein synthesis. BEP.indd Page 2 15/10/12 11:27 AM user-F408 /Users/user-F408/Desktop

1 2 H He 1.008 4.003

3 4 5 6 7 8 9 10 Li Be B C N O F Ne 6.94 9.01 10.81 12.011 14.01 16.00 19.00 20.18

11 12 13 14 15 16 17 18 Na Mg Al Si P S Cl Ar 22.99 24.31 26.98 28.09 30.97 32.06 35.45 39.95

19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 K Ca Sc Ti V Cr Mn Fe Co Ni Cu Zn Ga Ge As Se Br Kr 39.10 40.08 44.96 47.90 50.94 52.00 54.94 55.85 58.93 58.71 63.55 65.37 69.72 72.59 74.92 78.96 79.90 83.30

37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 Rb Sr Y Zr Nb Mo Te Ru Rh Pd Ag Cd In Sn Sb Te I Xe 85.47 87.62 88.91 91.22 92.91 95.94 98.91 101.07 102.91 106.4 107.87 112.40 114.82 118.69 121.75 126.70 126.90 131.30

55 56 57–70 71 72 73 74 75 76 77 78 79 80 81 82 83 84 85 86 Cs Ba * Lu Hf Ta W Re Os Ir Pt Au Hg Tl Pb Bi Po At Rn 132.91 137.34 174.97 178.49 180.95 183.85 186.2 190.2 192.2 195.09 196.97 200.59 204.37 207.19 208.98 (209) (210) (222)

87 88 89–102 103 104 105 106 107 108 109 110 111 112 114 116 118 Fr Ra ** Lr Rf Db Sg Bh Hs Mt Uun Uuu Uub Uuq Uuh Uuo (223) 226.03 262.11 261.11 262.11 263.12 264.12 265.13 268 269 272 277 289 289 293

57 58 59 60 61 62 63 64 65 66 67 68 69 70 *Lanthanides La Ce Pr Nd Pm Sm Eu Gd Tb Dy Ho Er Tm Yb 138.91 140.12 140.91 144.24 144.91 150.36 151.96 157.25 158.93 162.50 164.93 167.26 168.93 173.04

89 90 91 92 93 94 95 96 97 98 99 100 101 102 **Actinides Ac Th Pa U Np Pu Am Cm Bk Cf Es Fm Md No 227.03 232.04 231.04 238.03 237.05 244.06 243.06 247.07 247.07 251.08 252.08 257.10 258.10 259.10

Some Conversion Factors Some Physical Constants, With Symbols and Values

Length 1 cm 10 mm 104 ␮m 107 nm Atomic mass unit amu 1.661 1024 g 108 Å 0.394 in (dalton) 1 in 2.54 cm Avogadro’s number N 6.022 1023/mol 1 yard 0.9144 meters 1 mile 1.609 kilometers Becquerel Bq 1 dps 23 Mass 1 g 103 kg 103 mg 106 ␮g Boltzmann constant k 1.381 10 J/K; 24 3.53 102 oz 3.298 10 cal/K 1 oz 28.3 g Curie Ci 3.70 1010 dps

Temperature °C 5/9(°F 32) Electron volt eV 1.602 1019 J; K °C 273 3.828 1020 cal

Energy 1 J 107 erg 0.239 cal Faraday constant 96,480 J/V • mol

1 cal 4.184 J Gas constant R 1.987 cal/mol • K; Pressure 1 torr 1 mm Hg 1.32 103 atm 8.315 J/mol • K 2 34 1.333 10 Pa Planck’s constant h 1.584 10 cal • s; 5 34 1 atm 758 torr 1.01 10 Pa 6.626 10 J • s Radioactivity 1 Ci 3.7 1010 dps 37 GBq Speed of light c 2.998 1010 cm/s 1,000 dpm 16.7 Bq (in vacuum) BEP.indd Page 3 15/10/12 11:27 AM user-F408 /Users/user-F408/Desktop

Unit Abbreviations

A ampere kJ kilojoule Å angstrom kPa kilopascal atm atmosphere L liter Bq becquerel M molar (concentration) C coulomb m meter °C degree Celsius mg milligram cal calorie min minute Ci curie mL milliliter cm centimeter mm millimeter cpm counts per minute mm Hg millimeters of mercury (pressure) Da dalton mol mole dm decimeter mV millivolt dpm disintegrations per minute ␮m micrometer dps disintegrations per second ␮mol micromole faraday N normal (concentration) G gauss nm nanometer g gram Pa pascal GBq gigabecquerel r revolution h hour S Svedberg unit J joule s second K kelvin V volt kcal kilocalorie yr year kDa kilodalton

Some Prefixes Used in the International System of Units Mathematical Constants

109 giga G 103 milli m ␲ 3.1416 106 mega M 106 micro ␮ e 2.718 3 9 10 kilo k 10 nano n ln x 2.303 log10 x 101 deci d 1012 pico p 102 centi c 1015 femto f